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Armstrong EE, Li C, Campana MG, Ferrari T, Kelley JL, Petrov DA, Solari KA, Mooney JA. A Pipeline and Recommendations for Population and Individual Diagnostic SNP Selection in Non-Model Species. Mol Ecol Resour 2025; 25:e14048. [PMID: 39611246 PMCID: PMC11887608 DOI: 10.1111/1755-0998.14048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 10/16/2024] [Accepted: 11/06/2024] [Indexed: 11/30/2024]
Abstract
Despite substantial reductions in the cost of sequencing over the last decade, genetic panels remain relevant due to their cost-effectiveness and flexibility across a variety of sample types. In particular, single nucleotide polymorphism (SNP) panels are increasingly favoured for conservation applications. SNP panels are often used because of their adaptability, effectiveness with low-quality samples, and cost-efficiency for population monitoring and forensics. However, the selection of diagnostic SNPs for population assignment and individual identification can be challenging. The consequences of poor SNP selection are under-powered panels, inaccurate results, and monetary loss. Here, we develop a novel and user-friendly SNP selection pipeline (mPCRselect) that can be used to select SNPs for population assignment and/or individual identification. mPCRselect allows any researcher, who has sufficient SNP-level data, to design a successful and cost-effective SNP panel for a diploid species of conservation concern.
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Affiliation(s)
- Ellie E. Armstrong
- School of Biological SciencesWashington State UniversityPullmanWashingtonUSA
- Department of Evolution, Ecology and Organismal BiologyUniversity of California, RiversideRiversideCaliforniaUSA
| | - Chenyang Li
- Department of Quantitative and Computational BiologyUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Michael G. Campana
- Smithsonian's National Zoo and Conservation Biology InstituteWashingtonDCUSA
| | - Tessa Ferrari
- Department of Quantitative and Computational BiologyUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Joanna L. Kelley
- Department of Ecology and Evolutionary BiologyUniversity of California, Santa CruzSanta CruzCaliforniaUSA
| | - Dmitri A. Petrov
- Department of BiologyStanford UniversityStanfordCaliforniaUSA
- Chan Zuckerberg BioHubSan FranciscoCaliforniaUSA
- Program for Conservation Genomics, Center for Computational, Evolutionary, and Human GenomicsStanfordCaliforniaUSA
| | | | - Jazlyn A. Mooney
- Department of Quantitative and Computational BiologyUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
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de Barros Rodrigues ML, Rodrigues MP, Norton HL, Mendes-Junior CT, Simões AL, Lawson DJ. Large-scale selection of highly informative microhaplotypes for ancestry inference and population specific informativeness. Forensic Sci Int Genet 2025; 74:103153. [PMID: 39378714 DOI: 10.1016/j.fsigen.2024.103153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 09/30/2024] [Accepted: 10/01/2024] [Indexed: 10/10/2024]
Abstract
Microhaplotypes (MHs) describe physically close genetic markers that are inherited together and are gaining prominence due to their efficiency in forensic, clinical, and population studies. They excel in kinship analysis, DNA mixture detection, and ancestry inference, offering advantages in precision over individual SNPs and STRs. In this study, a pipeline was developed to efficiently select highly informative MHs from large-scale genomic datasets. Over 120,000 MHs were identified from almost a million markers, which allow this non-independent information to be efficiently used for inference. The MHs were compared to SNPs in terms of their informativeness and performance of their subsets in ancestry inference and all the results consistently favored MHs. A method for ranking markers by specific population informativeness was also introduced, which showed improvement in the accuracy of Native American ancestry estimation, overcoming the challenges of its underrepresentation in datasets. In conclusion, this study presents a comprehensive way for selecting highly informative MHs for accurate ancestry inference. The proposed approach and the subsets selected by specific population informativeness offer valuable tools for improving ancestry inference accuracy, particularly for admixed populations as demonstrated for a Brazilian dataset.
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Affiliation(s)
- Maria Luisa de Barros Rodrigues
- Programa de Pós-Graduação em Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
| | | | - Heather L Norton
- Department of Anthropology, University of Cincinnati, Cincinnati, OH 45221, United States
| | - Celso Teixeira Mendes-Junior
- Departamento de Química, Laboratório de Pesquisas Forenses e Genômicas, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901, Brazil
| | - Aguinaldo Luiz Simões
- Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil
| | - Daniel John Lawson
- Institute of Statistical Sciences, School of Mathematics, Woodland Road, University of Bristol, Bristol BS8 1UG, UK; MRC Integrative Epidemiology Unit, School of Medicine, Oakfield Grove, University of Bristol, Bristol BS8 2BN, UK.
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Flores I, Torres-Reverón A, Navarro E, Nieves-Vázquez CI, Cotto-Vázquez AC, Alonso-Díaz JM, Bracero NJ, Vincent K. Uncovering moderators of pain perception by women with endometriosis from Latin America and Spain: the roles of sociodemographics, racial self-identity, and pain catastrophizing. Pain 2024; 165:2111-2118. [PMID: 38564184 PMCID: PMC11333178 DOI: 10.1097/j.pain.0000000000003230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 02/13/2024] [Indexed: 04/04/2024]
Abstract
ABSTRACT A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis.
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Affiliation(s)
- Idhaliz Flores
- Department of Basic Sciences, Ponce Health Sciences University, Ponce, PR
- Department of Obstetrics and Gynecology, Ponce Health Sciences University, Ponce, PR
- Sur180 Therapeutics, LLC, McAllen, TX
| | - Annelyn Torres-Reverón
- Department of Basic Sciences, Ponce Health Sciences University, Ponce, PR
- Sur180 Therapeutics, LLC, McAllen, TX
| | - Eduardo Navarro
- Department of Basic Sciences, Ponce Health Sciences University, Ponce, PR
| | | | | | | | - Nabal J. Bracero
- Department of Obstetrics and Gynecology, University of Puerto Rico
| | - Katy Vincent
- Nuffield Department of Women’s & Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, UK
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Piekos JA, Amorim G, Ridolfi F, Cordeiro-Santos M, Kritski AL, Figueiredo MC, Andrade BB, Santos AR, Haas DW, Sterling TR, Rolla VC, Edwards DRV. Genetic ancestry proportion influences risk of adverse events from tuberculosis treatment in Brazil. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.08.29.24312595. [PMID: 39252933 PMCID: PMC11383467 DOI: 10.1101/2024.08.29.24312595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
Tuberculosis (TB) treatment is highly effective, but response to therapy can vary by geography, race, and ethnicity. We assessed for differences in TB treatment response in a representative and heterogeneous Brazilian population. We estimated genetic ancestry proportion according to major ancestry groups (African, European, and Amerindian ancestry) in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort. RePORT-Brazil is an observational prospective cohort study of individuals with newly-diagnosed, culture-confirmed, pulmonary TB. TB treatment outcomes that were attributed to TB treatment included Grade 2 or higher adverse drug reaction (ADR), Grade 3 or higher ADR, hepatic ADR, and failure/recurrence. Ancestry proportion was the main predictor in logistic regression for each outcome, with adjustments for candidate confounders. There were 941 pulmonary TB patients included in this study. We observed a decreased risk of Grade 2+ ADR when African ancestry proportion increased by 10% (Odds Ratio [OR] 0.41, 95% Confidence Interval [CI] 0.20 -0.85) and an increased risk for Grade 2+ ADR with increasing European ancestry (OR 2.84, 95% CI 1.47 - 5.48). We then performed the same analysis adding HIV status as an interaction term. The decreased risk for Grade 2+ ADR seen for African ancestry proportion did not hold for persons living with HIV; we observed increased risk for Grade 2+ ADR with increasing African ancestry proportion. There were no associations with Amerindian ancestry or for other treatment outcomes. In this Brazilian TB cohort, toxicity risk was associated with African and European ancestry, divergent, and affected by HIV. #RePORT-Brazil Consortium members include: Aline Benjamin and Flavia M. Sant'Anna Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil Jamile Garcia de Oliveira and João Marine Clínica de Saúde Rinaldo Delmare, Rio de Janeiro, Brazil Adriana Rezende and Anna Cristina Carvalho Secretaria de Saúde de Duque de Caxias, Rio de Janeiro, Brazil Michael Rocha and Betânia Nogueira Instituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil Alexandra Brito and Renata Spener Fundação Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil Megan Turner Vanderbilt University Medical Center, Nashville, USA.
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Penedo FJ, Moreno PI, Pons M, Pinheiro PS, Antoni MH, Lopes G, Calfa C, Chalela P, Garcini L, Wang CP, Chen Y, Diaz A, Cole S, Ramirez AG. Avanzando Caminos (Leading Pathways): design and procedures of the Hispanic/Latino Cancer Survivorship Study. Am J Epidemiol 2024; 193:940-950. [PMID: 38576195 PMCID: PMC11466847 DOI: 10.1093/aje/kwae033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/27/2024] [Accepted: 03/29/2024] [Indexed: 04/06/2024] Open
Abstract
Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress-related, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. Avanzando Caminos is a prospective, cohort-based study of 3000 Hispanics/Latinos who completed primary cancer treatment within the past 5 years that is representative of the general Hispanic/Latino population in the United States. Participants will complete self-report measures at baseline (time [T] 1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood samples drawn for assessment of leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. Avanzando Caminos will fill critical gaps in knowledge in order to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.
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Affiliation(s)
- Frank J Penedo
- Department of Psychology, College of Arts and Sciences, University of Miami, Coral Gables, FL 33124, United States
- Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
- Cancer Control Research Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, United States
| | - Patricia I Moreno
- Cancer Control Research Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, United States
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
| | - Magela Pons
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
| | - Paulo S Pinheiro
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
| | - Michael H Antoni
- Department of Psychology, College of Arts and Sciences, University of Miami, Coral Gables, FL 33124, United States
- Cancer Control Research Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, United States
| | - Gilberto Lopes
- Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
| | - Carmen Calfa
- Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, United States
| | - Patricia Chalela
- Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX 78229, United States
- Department of Population Health Sciences, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Luz Garcini
- Department of Psychological Sciences, School of Social Sciences, Rice University, Houston, TX 77005, United States
| | - Chen-Pin Wang
- Department of Population Health Sciences, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Yidong Chen
- Department of Population Health Sciences, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Adolfo Diaz
- Department of Medicine, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Steve Cole
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, United States
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, United States
| | - Amelie G Ramirez
- Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX 78229, United States
- Department of Population Health Sciences, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, United States
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Dalmasso MC, de Rojas I, Olivar N, Muchnik C, Angel B, Gloger S, Sanchez Abalos MS, Chacón MV, Aránguiz R, Orellana P, Cuesta C, Galeano P, Campanelli L, Novack GV, Martinez LE, Medel N, Lisso J, Sevillano Z, Irureta N, Castaño EM, Montrreal L, Thoenes M, Hanses C, Heilmann‐Heimbach S, Kairiyama C, Mintz I, Villella I, Rueda F, Romero A, Wukitsevits N, Quiroga I, Gona C, Lambert J, Solis P, Politis DG, Mangone CA, Gonzalez‐Billault C, Boada M, Tàrraga L, Slachevsky A, Albala C, Fuentes P, Kochen S, Brusco LI, Ruiz A, Morelli L, Ramírez A. The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease. Alzheimers Dement 2024; 20:1298-1308. [PMID: 37985413 PMCID: PMC10917041 DOI: 10.1002/alz.13522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 09/28/2023] [Accepted: 10/01/2023] [Indexed: 11/22/2023]
Abstract
INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. HIGHLIGHTS This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.
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Affiliation(s)
| | - Itziar de Rojas
- Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de CatalunyaBarcelonaSpain
- CIBERNED, Network Center for Biomedical Research in Neurodegenerative DiseasesNational Institute of Health Carlos IIIMadridSpain
| | - Natividad Olivar
- Center of Neuropsychiatry and Neurology of BehaviorSchool of MedicineUniversity of Buenos AiresBuenos AiresArgentina
| | - Carolina Muchnik
- Center of Neuropsychiatry and Neurology of BehaviorSchool of MedicineUniversity of Buenos AiresBuenos AiresArgentina
| | - Bárbara Angel
- Public Health Nutrition UnitInstitute of Nutrition and Food TechnologyUniversity of ChileSantiagoChile
- Interuniversity Center for Healthy Aging RED21993SantiagoChile
| | - Sergio Gloger
- Biomedica Research GroupCentro de Estudios ClínicosSantiagoChile
- Departamento de Psiquiatría y Salud MentalCampus Oriente, Facultad de MedicinaUniversidad de ChileSantiagoChile
| | | | | | - Rafael Aránguiz
- Biomedica Research GroupCentro de Estudios ClínicosSantiagoChile
- Instituto Nacional de GeriatríaSantiagoChile
| | - Paulina Orellana
- Geroscience Center for Brain Health and MetabolismSantiagoChile
- Latin American Institute for Brain Health (BrainLat)Universidad Adolfo IbanezSantiagoChile
- Center for Social and Cognitive Neuroscience (CSCN)School of PsychologyUniversidad Adolfo IbanezSantiagoChile
| | - Carolina Cuesta
- Hospital Interzonal General de Agudos‐Eva PerónSan MartínArgentina
| | - Pablo Galeano
- Laboratory of Brain Aging and Neurodegeneration, Fundacion Instituto Leloir‐IIBBABuenos AiresArgentina
| | - Lorenzo Campanelli
- Laboratory of Brain Aging and Neurodegeneration, Fundacion Instituto Leloir‐IIBBABuenos AiresArgentina
| | - Gisela Vanina Novack
- Laboratory of Brain Aging and Neurodegeneration, Fundacion Instituto Leloir‐IIBBABuenos AiresArgentina
| | | | - Nancy Medel
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Julieta Lisso
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Zulma Sevillano
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Nicolás Irureta
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Eduardo Miguel Castaño
- Laboratory of Brain Aging and Neurodegeneration, Fundacion Instituto Leloir‐IIBBABuenos AiresArgentina
| | - Laura Montrreal
- Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de CatalunyaBarcelonaSpain
| | - Michaela Thoenes
- Division of Neurogenetics and Molecular PsychiatryDepartment of Psychiatry and PsychotherapyFaculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany
| | - Claudia Hanses
- Department of Psychiatry and PsychotherapyUniversity Hospital of BonnBonnGermany
| | | | | | - Inés Mintz
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Ivana Villella
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Fabiana Rueda
- Imaging Diagnostics ServiceHospital El CruceFlorencio VarelaArgentina
| | - Amanda Romero
- Imaging Diagnostics ServiceHospital El CruceFlorencio VarelaArgentina
| | - Nancy Wukitsevits
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Ivana Quiroga
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Cristian Gona
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | - Jean‐Charles Lambert
- Université de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167‐RID‐AGE, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissementLilleFrance
| | - Patricia Solis
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
- Asistencia Medica IntegralHospital El CruceFlorencio VarelaArgentina
| | | | | | - Christian Gonzalez‐Billault
- Geroscience Center for Brain Health and MetabolismSantiagoChile
- Faculty of SciencesUniversity of ChileSantiagoChile
| | - Mercè Boada
- Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de CatalunyaBarcelonaSpain
- CIBERNED, Network Center for Biomedical Research in Neurodegenerative DiseasesNational Institute of Health Carlos IIIMadridSpain
| | - Lluís Tàrraga
- Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de CatalunyaBarcelonaSpain
- CIBERNED, Network Center for Biomedical Research in Neurodegenerative DiseasesNational Institute of Health Carlos IIIMadridSpain
| | - Andrea Slachevsky
- Faculty of SciencesUniversity of ChileSantiagoChile
- Neuropsychology and Clinical Neuroscience Laboratory (LANNEC)Physiopathology Department ‐ Intitute of Biomedical Sciences (ICBM)Neuroscience and East Neuroscience DepartmentsFaculty of MedicineUniversity of ChileSantiagoChile
- Memory and Neuropsychiatric Center (CMYN)Memory Unit ‐ Neurology DepartmentHospital del Salvador and Faculty of MedicineUniversity of ChileSantiagoChile
- Departamento de Neurología y PsiquiatríaClínica Alemana‐Universidad del DesarrolloSantiagoChile
| | - Cecilia Albala
- Public Health Nutrition UnitInstitute of Nutrition and Food TechnologyUniversity of ChileSantiagoChile
- Interuniversity Center for Healthy Aging RED21993SantiagoChile
| | - Patricio Fuentes
- Geriatrics Section Clinical Hospital University of ChileSantiagoChile
- Neurology Service Hospital del SalvadorSantiagoChile
| | - Silvia Kochen
- Studies in Neuroscience and Complex Systems Unit‐CONICET‐HEC‐UNAJFlorencio VarelaArgentina
| | - Luis Ignacio Brusco
- Center of Neuropsychiatry and Neurology of BehaviorSchool of MedicineUniversity of Buenos AiresBuenos AiresArgentina
| | - Agustín Ruiz
- Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de CatalunyaBarcelonaSpain
- CIBERNED, Network Center for Biomedical Research in Neurodegenerative DiseasesNational Institute of Health Carlos IIIMadridSpain
| | - Laura Morelli
- Laboratory of Brain Aging and Neurodegeneration, Fundacion Instituto Leloir‐IIBBABuenos AiresArgentina
| | - Alfredo Ramírez
- Division of Neurogenetics and Molecular PsychiatryDepartment of Psychiatry and PsychotherapyFaculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany
- University of Bonn Medical CenterDepartment of Neurodegenerative Disease and Geriatric PsychiatryBonnGermany
- German Center for Neurodegenerative Diseases (DZNE)BonnGermany
- Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD)University of CologneCologneGermany
- Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative DiseasesSan AntonioTexasUSA
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Leon C, Manley E, Neely AM, Castillo J, Ramos Correa M, Velarde DA, Yang M, Puente PE, Romero DI, Ren B, Chai W, Gladstone M, Lamango NS, Huang Y, Offringa IA. Lack of racial and ethnic diversity in lung cancer cell lines contributes to lung cancer health disparities. Front Oncol 2023; 13:1187585. [PMID: 38023251 PMCID: PMC10651223 DOI: 10.3389/fonc.2023.1187585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Lung cancer is the leading cause of cancer death in the United States and worldwide, and a major source of cancer health disparities. Lung cancer cell lines provide key in vitro models for molecular studies of lung cancer development and progression, and for pre-clinical drug testing. To ensure health equity, it is imperative that cell lines representing different lung cancer histological types, carrying different cancer driver genes, and representing different genders, races, and ethnicities should be available. This is particularly relevant for cell lines from Black men, who experience the highest lung cancer mortality in the United States. Here, we undertook a review of the available lung cancer cell lines and their racial and ethnic origin. We noted a marked imbalance in the availability of cell lines from different races and ethnicities. Cell lines from Black patients were strongly underrepresented, and we identified no cell lines from Hispanic/Latin(x) (H/L), American Indian/American Native (AI/AN), or Native Hawaiian or other Pacific Islander (NHOPI) patients. The majority of cell lines were derived from White and Asian patients. Also missing are cell lines representing the cells-of-origin of the major lung cancer histological types, which can be used to model lung cancer development and to study the effects of environmental exposures on lung tissues. To our knowledge, the few available immortalized alveolar epithelial cell lines are all derived from White subjects, and the race and ethnicity of a handful of cell lines derived from bronchial epithelial cells are unknown. The lack of an appropriately diverse collection of lung cancer cell lines and lung cancer cell-of-origin lines severely limits racially and ethnically inclusive lung cancer research. It impedes the ability to develop inclusive models, screen comprehensively for effective compounds, pre-clinically test new drugs, and optimize precision medicine. It thereby hinders the development of therapies that can increase the survival of minority and underserved patients. The noted lack of cell lines from underrepresented groups should constitute a call to action to establish additional cell lines and ensure adequate representation of all population groups in this critical pre-clinical research resource.
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Affiliation(s)
- Christopher Leon
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | | | - Aaron M. Neely
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Jonathan Castillo
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Michele Ramos Correa
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Diego A. Velarde
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Minxiao Yang
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Pablo E. Puente
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Diana I. Romero
- Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, United States
| | - Bing Ren
- Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, United States
| | - Wenxuan Chai
- Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, United States
| | - Matthew Gladstone
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Nazarius S. Lamango
- College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL, United States
| | - Yong Huang
- Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, United States
| | - Ite A. Offringa
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
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8
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Figueroa MAC, Lujambio IM, Gutiérrez TA, Hernández MFP, Ramírez EYE, Guzmán DJ, Sánchez MFL, Morales HFG, Samudio HJG, Sánchez FS, Flores MD, Zamarripa CAJ, Mendoza CCC, Hernández MEO, Velázquez CMO, Flores MS, Orozco DVH, Moreno GYC, Cruz M, de Jesús Peralta Romero J. Association of the rs5186 polymorphism of the AGTR1 gene with decreased eGFR in patients with type 2 diabetes from Mexico City. Nefrologia 2023; 43:546-561. [PMID: 37996337 DOI: 10.1016/j.nefroe.2022.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 06/10/2022] [Accepted: 06/29/2022] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Early biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years. The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. OBJECTIVE The aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. METHODS We analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student's t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p<0.05. Data was analyzed using Statistical Package STATA v11 software. RESULTS Dominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05-3.39, p=0.031) and 2.01 (1.08-3.73, p=0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10-5.89) in women in Over-dominant model. CONCLUSION In clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.
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Affiliation(s)
- Manuel Alejandro Contreras Figueroa
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México
| | - Irene Mendoza Lujambio
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México
| | - Teresa Alvarado Gutiérrez
- Coordinación Clínica de Educación e Investigación en Salud de la Unidad de Medicina Familiar 31, Instituto Mexicano del Seguro Social, Delegación sur, Ciudad de México, México
| | - María Fernanda Pérez Hernández
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México; Red de Medicina Para la Educación, el Desarrollo y la Investigación Científica de Iztacala. MEDICI, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, México
| | - Evelyn Yazmín Estrada Ramírez
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Departamento de Nefrología del Hospital de Especialidades "Dr. Antonio Fraga Mouret", CMN La Raza, IMSS, Ciudad de México, México
| | - Dominga Jiménez Guzmán
- Departamento de Nefrología del Hospital de Especialidades "Dr. Bernardo Sepúlveda" CMN Siglo XXI, IMSS, Ciudad de México, México; Jefatura de la Unidad de Consulta Externa de la UMAE, Hospital de Alta Especialidad Médica "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - María Fernanda Lucas Sánchez
- Secretaría de Enseñanza Clínica, Internado y Servicio Social. Facultad de Medicina UNAM, Ciudad de México, México; Becaria de la Dirección General de Calidad y Educación en Salud, Secretaría de Salud, México
| | - Hannia Fernanda González Morales
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Red de Medicina Para la Educación, el Desarrollo y la Investigación Científica de Iztacala. MEDICI, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, México
| | - Héctor Jaime Gómez Samudio
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - Fernando Suarez Sánchez
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - Margarita Díaz Flores
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - Carlos Alberto Jiménez Zamarripa
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México
| | - Claudia Camelia Calzada Mendoza
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México
| | - María Esther Ocharán Hernández
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México
| | - Cora Mariana Orozco Velázquez
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Secretaría de Enseñanza Clínica, Internado y Servicio Social. Facultad de Medicina UNAM, Ciudad de México, México
| | - Mariana Soto Flores
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Departamento de Formación Integral e Institucional, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Ciudad de México, México
| | - Daniela Vicenta Hernández Orozco
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México; Departamento de Formación Integral e Institucional, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Ciudad de México, México
| | - Gabriela Yanet Cortés Moreno
- Coordinación Nacional de Investigación, Subdirección de Servicios de salud de Petróleos Mexicanos, PEMEX, Ciudad de México, México
| | - Miguel Cruz
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - José de Jesús Peralta Romero
- Unidad de Investigación Médica en Bioquímica, Unidad Médica de Alta Especialidad "Dr. Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México.
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9
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Horimoto AR, Boyken LA, Blue EE, Grinde KE, Nafikov RA, Sohi HK, Nato AQ, Bis JC, Brusco LI, Morelli L, Ramirez A, Dalmasso MC, Temple S, Satizabal C, Browning SR, Seshadri S, Wijsman EM, Thornton TA. Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations. HGG ADVANCES 2023; 4:100207. [PMID: 37333771 PMCID: PMC10276158 DOI: 10.1016/j.xhgg.2023.100207] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 05/16/2023] [Indexed: 06/20/2023] Open
Abstract
Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer's Genetics in Argentina-Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.
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Affiliation(s)
| | - Lisa A. Boyken
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
| | - Elizabeth E. Blue
- Division of Medical Genetics/Department of Medicine, University of Washington, Seattle, WA 98195, USA
- Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA
| | - Kelsey E. Grinde
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
- Department of Mathematics, Statistics and Computer Science, Macalester College, Saint Paul, MN 55105, USA
| | - Rafael A. Nafikov
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
- Division of Medical Genetics/Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Harkirat K. Sohi
- Division of Medical Genetics/Department of Medicine, University of Washington, Seattle, WA 98195, USA
- Biomedical and Health Informatics Program, University of Washington, Seattle, WA 98195, USA
| | - Alejandro Q. Nato
- Division of Medical Genetics/Department of Medicine, University of Washington, Seattle, WA 98195, USA
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
| | - Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA
| | - Luis I. Brusco
- CENECON - Center of Behavioural Neurology and Neuropsychiatry, School of Medicine, University of Buenos Aires, C1121A6B Buenos Aires, Argentina
| | - Laura Morelli
- Laboratory of Brain Aging and Neurodegeneration-Fundación Instituto Leloir-IIBBA- National Scientific and Technical Research Council (CONICET), C1405BWE Ciudad Autónoma de Buenos Aires, Argentina
| | - Alfredo Ramirez
- Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937 Cologne, Germany
- Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127 Bonn, Germany
- German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) University of Cologne, 50674 Cologne, Germany
- Department of Psychiatry, UT Health San Antonio, San Antonio, TX 78229, USA
- Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA
| | - Maria Carolina Dalmasso
- Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937 Cologne, Germany
- Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce, National University A. Jauretche (UNAJ), B1888AAE Florencio Varela, Argentina
| | - Seth Temple
- Department of Statistics, University of Washington, Seattle, WA 98195, USA
| | - Claudia Satizabal
- Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA
- Department of Population Health Sciences, University of Texas, San Antonio, TX 78229, USA
- Department of Neurology, University of Texas, San Antonio, TX 78229, USA
| | - Sharon R. Browning
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
| | - Sudha Seshadri
- Department of Neurology, University of Texas, San Antonio, TX 78229, USA
| | - Ellen M. Wijsman
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
- Division of Medical Genetics/Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Timothy A. Thornton
- Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
- Department of Statistics, University of Washington, Seattle, WA 98195, USA
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10
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Gaudin RGN, Figueiro G, Flores-Gutiérrez S, Mut P, Vega-Requena Y, Luna-Andrada L, Ackermann E, Hidalgo PC, Carracedo A, Torres M, Sans M. DNA polymorphisms associated with lactase persistence, self-perceived symptoms of lactose intolerance, milk and dairy consumption, and ancestry, in the Uruguayan population. Am J Hum Biol 2023; 35:e23868. [PMID: 36695417 DOI: 10.1002/ajhb.23868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
Uruguay has one of the highest per capita milk intakes worldwide, even with a limited supply of lactose-free products; furthermore, the admixed nature of its population is well known, and various frequencies of lactase persistence (LP) are observed in the source populations. We aimed to contribute to the understanding of the relation between allelic variants associated with LP, milk consumption, digestive symptoms, and genetic ancestry in the Uruguayan population. Samples of saliva or peripheral blood were collected from 190 unrelated individuals from two regions of Uruguay, genotypes for polymorphic sites in a fragment within the LCT enhancer were determined and allelic frequencies calculated in all of them. Data were collected on frequency of milk and dairy consumption and self-reported symptoms in a subsample of 153 individuals. Biparental and maternal ancestry was determined by analyzing individual ancestry markers and mitochondrial DNA. Twenty-nine percentage of individuals reported symptoms attributed to the ingestion of fresh milk, with abdominal pain, bloating and flatulence being the most frequent. European LP-associated allele T-13910 showed a frequency of 33%, while other LP-associated alleles like G-13915 and T-14011 were observed in very low frequencies. Associations between self-reported symptoms, fresh milk intake, and C/T-13910 genotype were statistically significant. No evidence of association between genetic ancestry and C/T-13910 was found, although individuals carrying one T-13910 allele appeared to have more European ancestry. In conclusion, the main polymorphism capable of predicting lactose intolerance in Uruguayans is C/T-13910, although more studies are required to unravel the relation between genotype and lactase activity, especially in heterozygotes.
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Affiliation(s)
- Raúl Germán Negro Gaudin
- Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay
| | - Gonzalo Figueiro
- Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay
| | - Sara Flores-Gutiérrez
- Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay
| | - Patricia Mut
- Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay
| | - Yasser Vega-Requena
- Polo de Desarrollo Universitario Diversidad Genética Humana, Centro Universitario Regional Noreste, Tacuarembó, Universidad de la República, Montevideo, Uruguay
| | - Lorena Luna-Andrada
- Polo de Desarrollo Universitario Diversidad Genética Humana, Centro Universitario Regional Noreste, Tacuarembó, Universidad de la República, Montevideo, Uruguay
| | - Elizabeth Ackermann
- Polo de Desarrollo Universitario Diversidad Genética Humana, Centro Universitario Regional Noreste, Tacuarembó, Universidad de la República, Montevideo, Uruguay
| | - Pedro C Hidalgo
- Polo de Desarrollo Universitario Diversidad Genética Humana, Centro Universitario Regional Noreste, Tacuarembó, Universidad de la República, Montevideo, Uruguay
| | - Angel Carracedo
- Grupo de Medicina Xenómica, Centro en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
- Fundación Pública Galega de Medicina Xenómica (SERGAS)-CIBERER, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
| | - María Torres
- Fundación Pública Galega de Medicina Xenómica (SERGAS)-CIBERER, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
| | - Mónica Sans
- Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, Universidad de la República, Montevideo, Uruguay
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11
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Kayser M, Branicki W, Parson W, Phillips C. Recent advances in Forensic DNA Phenotyping of appearance, ancestry and age. Forensic Sci Int Genet 2023; 65:102870. [PMID: 37084623 DOI: 10.1016/j.fsigen.2023.102870] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/04/2023] [Indexed: 04/09/2023]
Abstract
Forensic DNA Phenotyping (FDP) comprises the prediction of a person's externally visible characteristics regarding appearance, biogeographic ancestry and age from DNA of crime scene samples, to provide investigative leads to help find unknown perpetrators that cannot be identified with forensic STR-profiling. In recent years, FDP has advanced considerably in all of its three components, which we summarize in this review article. Appearance prediction from DNA has broadened beyond eye, hair and skin color to additionally comprise other traits such as eyebrow color, freckles, hair structure, hair loss in men, and tall stature. Biogeographic ancestry inference from DNA has progressed from continental ancestry to sub-continental ancestry detection and the resolving of co-ancestry patterns in genetically admixed individuals. Age estimation from DNA has widened beyond blood to more somatic tissues such as saliva and bones as well as new markers and tools for semen. Technological progress has allowed forensically suitable DNA technology with largely increased multiplex capacity for the simultaneous analysis of hundreds of DNA predictors with targeted massively parallel sequencing (MPS). Forensically validated MPS-based FDP tools for predicting from crime scene DNA i) several appearance traits, ii) multi-regional ancestry, iii) several appearance traits together with multi-regional ancestry, and iv) age from different tissue types, are already available. Despite recent advances that will likely increase the impact of FDP in criminal casework in the near future, moving reliable appearance, ancestry and age prediction from crime scene DNA to the level of detail and accuracy police investigators may desire, requires further intensified scientific research together with technical developments and forensic validations as well as the necessary funding.
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Affiliation(s)
- Manfred Kayser
- Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | - Wojciech Branicki
- Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland,; Institute of Forensic Research, Kraków, Poland
| | - Walther Parson
- Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria; Forensic Science Program, The Pennsylvania State University, PA, USA
| | - Christopher Phillips
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain
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12
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Valverde-Hernández JC, Flores-Cruz A, Chavarría-Soley G, Silva de la Fuente S, Campos-Sánchez R. Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes. Front Genet 2023; 14:1114774. [PMID: 37065472 PMCID: PMC10098023 DOI: 10.3389/fgene.2023.1114774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/14/2023] [Indexed: 04/18/2023] Open
Abstract
Dyslipidemias are risk factors in diseases of significant importance to public health, such as atherosclerosis, a condition that contributes to the development of cardiovascular disease. Unhealthy lifestyles, the pre-existence of diseases, and the accumulation of genetic variants in some loci contribute to the development of dyslipidemia. The genetic causality behind these diseases has been studied primarily on populations with extensive European ancestry. Only some studies have explored this topic in Costa Rica, and none have focused on identifying variants that can alter blood lipid levels and quantifying their frequency. To fill this gap, this study focused on identifying variants in 69 genes involved in lipid metabolism using genomes from two studies in Costa Rica. We contrasted the allelic frequencies with those of groups reported in the 1000 Genomes Project and gnomAD and identified potential variants that could influence the development of dyslipidemias. In total, we detected 2,600 variants in the evaluated regions. However, after various filtering steps, we obtained 18 variants that have the potential to alter the function of 16 genes, nine variants have pharmacogenomic or protective implications, eight have high risk in Variant Effect Predictor, and eight were found in other Latin American genetic studies of lipid alterations and the development of dyslipidemia. Some of these variants have been linked to changes in blood lipid levels in other global studies and databases. In future studies, we propose to confirm at least 40 variants of interest from 23 genes in a larger cohort from Costa Rica and Latin American populations to determine their relevance regarding the genetic burden for dyslipidemia. Additionally, more complex studies should arise that include diverse clinical, environmental, and genetic data from patients and controls and functional validation of the variants.
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Affiliation(s)
| | - Andrés Flores-Cruz
- Centro de Investigación en Biología Celular y Molecular, University of Costa Rica, San José, Costa Rica
| | - Gabriela Chavarría-Soley
- Centro de Investigación en Biología Celular y Molecular, University of Costa Rica, San José, Costa Rica
- Escuela de Biología, University of Costa Rica, San José, Costa Rica
| | - Sandra Silva de la Fuente
- Centro de Investigación en Biología Celular y Molecular, University of Costa Rica, San José, Costa Rica
| | - Rebeca Campos-Sánchez
- Centro de Investigación en Biología Celular y Molecular, University of Costa Rica, San José, Costa Rica
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13
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Ruiz-Ramírez J, de la Puente M, Xavier C, Ambroa-Conde A, Álvarez-Dios J, Freire-Aradas A, Mosquera-Miguel A, Ralf A, Amory C, Katsara MA, Khellaf T, Nothnagel M, Cheung EYY, Gross TE, Schneider PM, Uacyisrael J, Oliveira S, Klautau-Guimarães MDN, Carvalho-Gontijo C, Pośpiech E, Branicki W, Parson W, Kayser M, Carracedo A, Lareu MV, Phillips C. Development and evaluations of the ancestry informative markers of the VISAGE Enhanced Tool for Appearance and Ancestry. Forensic Sci Int Genet 2023; 64:102853. [PMID: 36917866 DOI: 10.1016/j.fsigen.2023.102853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 02/15/2023] [Accepted: 03/02/2023] [Indexed: 03/07/2023]
Abstract
The VISAGE Enhanced Tool for Appearance and Ancestry (ET) has been designed to combine markers for the prediction of bio-geographical ancestry plus a range of externally visible characteristics into a single massively parallel sequencing (MPS) assay. We describe the development of the ancestry panel markers used in ET, and the enhanced analyses they provide compared to previous MPS-based forensic ancestry assays. As well as established autosomal single nucleotide polymorphisms (SNPs) that differentiate sub-Saharan African, European, East Asian, South Asian, Native American, and Oceanian populations, ET includes autosomal SNPs able to efficiently differentiate populations from Middle East regions. The ability of the ET autosomal ancestry SNPs to distinguish Middle East populations from other continentally defined population groups is such that characteristic patterns for this region can be discerned in genetic cluster analysis using STRUCTURE. Joint cluster membership estimates showing individual co-ancestry that signals North African or East African origins were detected, or cluster patterns were seen that indicate origins from central and Eastern regions of the Middle East. In addition to an augmented panel of autosomal SNPs, ET includes panels of 85 Y-SNPs, 16 X-SNPs and 21 autosomal Microhaplotypes. The Y- and X-SNPs provide a distinct method for obtaining extra detail about co-ancestry patterns identified in males with admixed backgrounds. This study used the 1000 Genomes admixed African and admixed American sample sets to fully explore these enhancements to the analysis of individual co-ancestry. Samples from urban and rural Brazil with contrasting distributions of African, European, and Native American co-ancestry were also studied to gauge the efficiency of combining Y- and X-SNP data for this purpose. The small panel of Microhaplotypes incorporated in ET were selected because they showed the highest levels of haplotype diversity amongst the seven population groups we sought to differentiate. Microhaplotype data was not formally combined with single-site SNP genotypes to analyse ancestry. However, the haplotype sequence reads obtained with ET from these loci creates an effective system for de-convoluting two-contributor mixed DNA. We made simple mixture experiments to demonstrate that when the contributors have different ancestries and the mixture ratios are imbalanced (i.e., not 1:1 mixtures) the ET Microhaplotype panel is an informative system to infer ancestry when this differs between the contributors.
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Affiliation(s)
- J Ruiz-Ramírez
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - M de la Puente
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
| | - C Xavier
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - A Ambroa-Conde
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - J Álvarez-Dios
- Faculty of Mathematics, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
| | - A Freire-Aradas
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - A Mosquera-Miguel
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - A Ralf
- Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, 3015 CN Rotterdam, South Holland, the Netherlands
| | - C Amory
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - M A Katsara
- Cologne Center for Genomics, University of Cologne, 50823 Cologne, Germany
| | - T Khellaf
- Cologne Center for Genomics, University of Cologne, 50823 Cologne, Germany
| | - M Nothnagel
- Cologne Center for Genomics, University of Cologne, 50823 Cologne, Germany; University Hospital Cologne, 50937 Cologne, Germany
| | - E Y Y Cheung
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany
| | - T E Gross
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany
| | - P M Schneider
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany
| | - J Uacyisrael
- Fiji Police Forensic Biology and DNA Laboratory, Nasova, Suva, Fiji
| | - S Oliveira
- Departamento Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brazil
| | | | - C Carvalho-Gontijo
- Departamento Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brazil
| | - E Pośpiech
- Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland
| | - W Branicki
- Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Kraków, Poland
| | - W Parson
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; Forensic Science Program, The Pennsylvania State University, University Park, State College, PA 16802, USA
| | - M Kayser
- Department of Genetic Identification, Erasmus MC, University Medical Center Rotterdam, 3015 CN Rotterdam, South Holland, the Netherlands
| | - A Carracedo
- Fundación Pública Galega de Medicina Xenómica (FPGMX), Instituto de Investigación Sanitaria (IDIS),15706 Santiago de Compostela, Spain; Genomics Group, CIBERER, CIMUS, University of Santiago de Compostela, Spain
| | - M V Lareu
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - C Phillips
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
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Bardan F, Higgins D, Austin JJ. A custom hybridisation enrichment forensic intelligence panel to infer biogeographic ancestry, hair and eye colour, and Y chromosome lineage. Forensic Sci Int Genet 2023; 63:102822. [PMID: 36525814 DOI: 10.1016/j.fsigen.2022.102822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 11/02/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022]
Abstract
Massively parallel sequencing can provide genetic data for hundreds to thousands of loci in a single assay for various types of forensic testing. However, available commercial kits require an initial PCR amplification of short-to-medium sized targets which limits their application for highly degraded DNA. Development and optimisation of large PCR multiplexes also prevents creation of custom panels that target different suites of markers for identity, biogeographic ancestry, phenotype, and lineage markers (Y-chromosome and mtDNA). Hybridisation enrichment, an alternative approach for target enrichment prior to sequencing, uses biotinylated probes to bind to target DNA and has proven successful on degraded and ancient DNA. We developed a customisable hybridisation capture method, that uses individually mixed baits to allow tailored and targeted enrichment to specific forensic questions of interest. To allow collection of forensic intelligence data, we assembled and tested a custom panel of hybridisation baits to infer biogeographic ancestry, hair and eye colour, and paternal lineage (and sex) on modern male and female samples with a range of self-declared ancestries and hair/eye colour combinations. The panel correctly estimated biogeographic ancestry in 9/12 samples (75%) but detected European admixture in three individuals from regions with admixed demographic history. Hair and eye colour were predicted correctly in 83% and 92% of samples respectively, where intermediate eye colour and blond hair were problematic to predict. Analysis of Y-chromosome SNPs correctly assigned sex and paternal haplogroups, the latter complementing and supporting biogeographic ancestry predictions. Overall, we demonstrate the utility of this hybridisation enrichment approach to forensic intelligence testing using a combined suite of biogeographic ancestry, phenotype, and Y-chromosome SNPs for comprehensive biological profiling.
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Affiliation(s)
- Felicia Bardan
- Australian Centre for Ancient DNA, School of Biological Sciences, The University of Adelaide, South Australia, Australia
| | - Denice Higgins
- Australian Centre for Ancient DNA, School of Biological Sciences, The University of Adelaide, South Australia, Australia; School of Dentistry, Health and Medical Sciences, The University of Adelaide, South Australia, Australia
| | - Jeremy J Austin
- Australian Centre for Ancient DNA, School of Biological Sciences, The University of Adelaide, South Australia, Australia.
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15
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Nierenberg JL, Adamson AW, Hu D, Huntsman S, Patrick C, Li M, Steele L, Tong B, Shieh Y, Fejerman L, Gruber SB, Haiman CA, John EM, Kushi LH, Torres-Mejía G, Ricker C, Weitzel JN, Ziv E, Neuhausen SL. Whole exome sequencing and replication for breast cancer among Hispanic/Latino women identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.01.25.23284924. [PMID: 36747679 PMCID: PMC9901069 DOI: 10.1101/2023.01.25.23284924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Introduction Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced Hispanic/Latina (H/L) women to identify BC susceptibility genes. Methods We conducted a pooled BC case-control analysis in H/L women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk. Results We saw a strong association of LoF variants in FANCM with ER-negative BC (p=4.1×10-7, OR [CI]: 6.7 [2.9-15.6]) and a nominal association with overall BC risk. Among known susceptibility genes, BRCA1 (p=2.3×10-10, OR [CI]: 24.9 [6.1-102.5]), BRCA2 (p=8.4×10-10, OR [CI]: 7.0 [3.5-14.0]), and PALB2 (p=1.8×10-8, OR [CI]: 6.5 [3.2-13.1]) were strongly associated with BC. There were nominally significant associations with CHEK2, RAD51D, and TP53. Conclusion In H/L women, LoF variants in FANCM were strongly associated with ER-negative breast cancer risk. It previously was proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested in clinical practice. Our results demonstrate that FANCM should be added to BC gene panels.
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Affiliation(s)
- Jovia L Nierenberg
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Aaron W Adamson
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
| | - Donglei Hu
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Scott Huntsman
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Carmina Patrick
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
| | - Min Li
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Linda Steele
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
| | - Barry Tong
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Yiwey Shieh
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Laura Fejerman
- Department of Public Health Service, University of California, Davis, Davis, CA, USA
- UC Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA, USA
| | - Stephen B Gruber
- Department of Medical Oncology and Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA
| | - Christopher A Haiman
- Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Esther M John
- Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA, USA
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Lawrence H Kushi
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | | | - Charité Ricker
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Elad Ziv
- Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Susan L Neuhausen
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
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16
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De Oliveira TC, Secolin R, Lopes-Cendes I. A review of ancestrality and admixture in Latin America and the caribbean focusing on native American and African descendant populations. Front Genet 2023; 14:1091269. [PMID: 36741309 PMCID: PMC9893294 DOI: 10.3389/fgene.2023.1091269] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 01/09/2023] [Indexed: 01/21/2023] Open
Abstract
Genomics can reveal essential features about the demographic evolution of a population that may not be apparent from historical elements. In recent years, there has been a significant increase in the number of studies applying genomic epidemiological approaches to understand the genetic structure and diversity of human populations in the context of demographic history and for implementing precision medicine. These efforts have traditionally been applied predominantly to populations of European origin. More recently, initiatives in the United States and Africa are including more diverse populations, establishing new horizons for research in human populations with African and/or Native ancestries. Still, even in the most recent projects, the under-representation of genomic data from Latin America and the Caribbean (LAC) is remarkable. In addition, because the region presents the most recent global miscegenation, genomics data from LAC may add relevant information to understand population admixture better. Admixture in LAC started during the colonial period, in the 15th century, with intense miscegenation between European settlers, mainly from Portugal and Spain, with local indigenous and sub-Saharan Africans brought through the slave trade. Since, there are descendants of formerly enslaved and Native American populations in the LAC territory; they are considered vulnerable populations because of their history and current living conditions. In this context, studying LAC Native American and African descendant populations is important for several reasons. First, studying human populations from different origins makes it possible to understand the diversity of the human genome better. Second, it also has an immediate application to these populations, such as empowering communities with the knowledge of their ancestral origins. Furthermore, because knowledge of the population genomic structure is an essential requirement for implementing genomic medicine and precision health practices, population genomics studies may ensure that these communities have access to genomic information for risk assessment, prevention, and the delivery of optimized treatment; thus, helping to reduce inequalities in the Western Hemisphere. Hoping to set the stage for future studies, we review different aspects related to genetic and genomic research in vulnerable populations from LAC countries.
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Affiliation(s)
- Thais C. De Oliveira
- Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil
| | - Rodrigo Secolin
- Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil
| | - Iscia Lopes-Cendes
- Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil
- The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil
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17
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Pilli E, Morelli S, Poggiali B, Alladio E. Biogeographical ancestry, variable selection, and PLS-DA method: a new panel to assess ancestry in forensic samples via MPS technology. Forensic Sci Int Genet 2023; 62:102806. [PMID: 36399972 DOI: 10.1016/j.fsigen.2022.102806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/14/2022]
Abstract
As evidenced by the large number of articles recently published in the literature, forensic scientists are making great efforts to infer externally visible features and biogeographical ancestry (BGA) from DNA analysis. Just as phenotypic, ancestry information obtained from DNA can provide investigative leads to identify the victims (missing/unidentified persons, crime/armed conflict/mass disaster victims) or trace their perpetrators when no matches were found with the reference profile or in the database. Recently, the advent of Massively Parallel Sequencing technologies associated with the possibility of harnessing high-throughput genetic data allowed us to investigate the associations between phenotypic and genomic variations in worldwide human populations and develop new BGA forensic tools capable of simultaneously analyzing up to millions of markers if for example the ancient DNA approach of hybridization capture was adopted to target SNPs of interest. In the present study, a selection of more than 3000 SNPs was performed to create a new BGA panel and the accuracy of the new panel to infer ancestry from unknown samples was evaluated by the PLS-DA method. Subsequently, the panel created was assessed using three variable selection techniques (Backward variable elimination, Genetic Algorithm and Regularized elimination procedure), and the best SNPs in terms of inferring bio-geographical ancestry at inter- and intra-continental level were selected to obtain panels to predict BGA with a reduced number of selected markers to be applied in routine forensic cases where PCR amplification is the best choice to target SNPs.
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Affiliation(s)
- Elena Pilli
- Department of Biology, Forensic Molecular Anthropology Laboratory, University of Florence, Florence, Italy
| | - Stefania Morelli
- Department of Biology, Forensic Molecular Anthropology Laboratory, University of Florence, Florence, Italy
| | - Brando Poggiali
- Department of Biology, Forensic Molecular Anthropology Laboratory, University of Florence, Florence, Italy
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18
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Challenges in selecting admixture models and marker sets to infer genetic ancestry in a Brazilian admixed population. Sci Rep 2022; 12:21240. [PMID: 36481695 PMCID: PMC9731996 DOI: 10.1038/s41598-022-25521-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 11/30/2022] [Indexed: 12/13/2022] Open
Abstract
The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.
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19
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Escobar-Castro K, Hernández-Zaragoza DI, Santizo A, Del Toro-Arreola S, Hernández E, Toledo S M. HLA molecular study of patients in a public kidney transplant program in Guatemala. Hum Immunol 2022; 83:741-748. [PMID: 36028459 DOI: 10.1016/j.humimm.2022.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 07/31/2022] [Accepted: 08/02/2022] [Indexed: 11/28/2022]
Abstract
Guatemala is a country located in Central America, and while it is one of the most populated countries in the region, the genetic diversity of the population has been poorly analyzed. Currently, there are no analyses of the distribution of human leukocyte antigen (HLA) system alleles in mixed ancestry (i.e., ladino) populations in Guatemala. The HLA system exhibits the most extensive polymorphism in the human genome and has been extensively analyzed in a large number of studies related to disease association, transplantation, and population genetics (with particular importance in the understanding of diversity in the human population). Here, we present HLA typing data from 127 samples of unrelated individuals from the kidney transplant program of the San Juan de Dios General Hospital (Guatemala City) using a PCR-SSOP-based (PCR-sequence specific oligonucleotide probes) typing method. We found 16 haplotypes that accounted for 39.76 % of the total haplotype diversity, of which thirteen have been reported previously in Native American populations and three have been reported in European populations. The analyses showed no deviations from Hardy-Weinberg equilibrium, and admixture estimates calculated with k = 3 ancestral components showed that Native American was the most represented component, followed by the European component. The African component was less prominent in the Guatemala mixed ancestry sample in comparison to samples from other countries in Central America. The HLA-based admixture results for Central America showed a continuum in the distribution of Native American, European and African ancestries throughout the region, which is consistent with the complex demographic history of the region.
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Affiliation(s)
- Karla Escobar-Castro
- Escuela de Estudios de Postgrado, Facultad de Ciencias Médicas, Universidad de San Carlos de Guatemala (USAC), Guatemala City, Guatemala; Laboratorio de Histocompatibilidad, Departamento de Nefrología y Trasplante, Hospital General San Juan de Dios, Guatemala City, Guatemala
| | - Diana Iraiz Hernández-Zaragoza
- Laboratorio de Genética Molecular, Escuela Nacional de Antropología e Historia (ENAH), Mexico City, Mexico; Unidad de Inmunogenética, Técnicas Genéticas Aplicadas a la Clínica (TGAC), Mexico City, Mexico.
| | - Adolfo Santizo
- Laboratorio de Histocompatibilidad, Departamento de Nefrología y Trasplante, Hospital General San Juan de Dios, Guatemala City, Guatemala
| | - Susana Del Toro-Arreola
- Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario en Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - Elisa Hernández
- Laboratorio de Histocompatibilidad, Departamento de Nefrología y Trasplante, Hospital General San Juan de Dios, Guatemala City, Guatemala
| | - Manuel Toledo S
- Departamento de Nefrología y Trasplante, Hospital General San Juan de Dios, Guatemala City, Guatemala
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20
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Asociación del polimorfismo rs5186 del gen AGTR1 con disminución de la TFGe en pacientes con diabetes tipo 2 de la Ciudad de México. Nefrologia 2022. [DOI: 10.1016/j.nefro.2022.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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21
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Xu H, Fang Y, Zhao M, Lan Q, Mei S, Liu L, Bai X, Zhu B. Forensic Features and Genetic Structure Analyses of the Beijing Han Nationality Disclosed by a Self-Developed Panel Containing a Series of Ancestry Informative Deletion/Insertion Polymorphism Loci. Front Ecol Evol 2022. [DOI: 10.3389/fevo.2022.890153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The utilization of the ancestry informative markers to disclose the ancestral composition of a certain population and explore the genetic affinities between diverse populations is beneficial to inferring the biogeographic ancestry of unknown individuals and assisting in case detection, as well as avoiding the impacts of population stratification during genome-wide association analysis studies. In the present study, we applied an in-house ancestry informative deletion/insertion polymorphic multiplex amplification system to investigate the ancestral compositions of the Beijing Han population and analyze the genetic relationships between the Beijing Han population and 31 global reference populations. The results demonstrated that 32 loci of this self-developed panel containing 39 loci significantly contributed to the inference of genetic information for the Beijing Han population. The results of multiple population genetics statistical analyses indicated that the ancestral component and genetic architecture of the Beijing Han population were analogous to the reference East Asian populations, and that the Beijing Han population was genetically close to the reference East Asian populations.
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22
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Kim EY, Che Y, Dean HJ, Lorenzo-Redondo R, Stewart M, Keller CK, Whorf D, Mills D, Dulin NN, Kim T, Votoupal M, Walter M, Fernandez-Sesma A, Kim H, Wolinsky SM. Transcriptome-wide changes in gene expression, splicing, and lncRNAs in response to a live attenuated dengue virus vaccine. Cell Rep 2022; 38:110341. [PMID: 35139383 PMCID: PMC8994511 DOI: 10.1016/j.celrep.2022.110341] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/20/2021] [Accepted: 01/14/2022] [Indexed: 01/26/2023] Open
Abstract
The tetravalent dengue vaccine candidate, TAK-003, induces a functional antibody response, but the titers of antibodies against the four serotypes of the dengue virus (DENV) can vary. Here, through a transcriptomic analysis on whole blood collected from recipients of a two-dose schedule of TAK-003, we examine gene expression, splicing, and transcript isoform-level changes for both protein-coding and noncoding genes to broaden our understanding of the immune response. Our analysis reveals a dynamic pattern of vaccine-associated regulation of long noncoding RNAs (lncRNAs), differential splicing of interferon-stimulated gene exons, and gene expression changes related to multiple signaling pathways that detect viral infection. Co-expression networks isolate immune cell-type-related and interferon-response modules that represent specific biological processes that correlate with more robust antibody responses. These data provide insights into the early determinants of the variable immune response to the vaccine, highlighting the significance of splicing and isoform-level gene regulatory mechanisms in defining vaccine immunogenicity.
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Affiliation(s)
- Eun-Young Kim
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Yan Che
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | | | - Ramon Lorenzo-Redondo
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Michael Stewart
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Caroline K Keller
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Daniel Whorf
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Dawson Mills
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Nikita N Dulin
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Tiffany Kim
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Megan Votoupal
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Miriam Walter
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Ana Fernandez-Sesma
- Department of Microbiology and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Heejin Kim
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA
| | - Steven M Wolinsky
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60011, USA.
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23
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Evaluation of the VISAGE basic tool for appearance and ancestry inference using ForenSeq® chemistry on the MiSeq FGx® system. Forensic Sci Int Genet 2022; 58:102675. [DOI: 10.1016/j.fsigen.2022.102675] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/13/2022] [Accepted: 02/01/2022] [Indexed: 11/04/2022]
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24
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Bateman NW, Tarney CM, Abulez TS, Hood BL, Conrads KA, Zhou M, Soltis AR, Teng PN, Jackson A, Tian C, Dalgard CL, Wilkerson MD, Kessler MD, Goecker Z, Loffredo J, Shriver CD, Hu H, Cote M, Parker GJ, Segars J, Al-Hendy A, Risinger JI, Phippen NT, Casablanca Y, Darcy KM, Maxwell GL, Conrads TP, O'Connor TD. Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry. iScience 2021; 25:103665. [PMID: 35036865 PMCID: PMC8753123 DOI: 10.1016/j.isci.2021.103665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 10/29/2021] [Accepted: 12/17/2021] [Indexed: 02/07/2023] Open
Abstract
Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single-nucleotide polymorphisms encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2 = 0.99). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma tissues combined resulted in the quantitation of 62 pAIMs that correlate with patient race and genotype-confirmed ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. pAIMs will support generalized proteoancestry assessment as well as efforts investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
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Affiliation(s)
- Nicholas W. Bateman
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA,Corresponding author 3289 Woodburn Rd, Suite 375, Annandale, VA 22003;
| | - Christopher M. Tarney
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Tamara S. Abulez
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - Brian L. Hood
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - Kelly A. Conrads
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - Ming Zhou
- Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Anthony R. Soltis
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA,The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
| | - Pang-Ning Teng
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - Amanda Jackson
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Chunqiao Tian
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - Clifton L. Dalgard
- The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA,Department of Anatomy Physiology and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Matthew D. Wilkerson
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA,The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA,Department of Anatomy Physiology and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
| | - Michael D. Kessler
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Zachary Goecker
- University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
| | - Jeremy Loffredo
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Craig D. Shriver
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Hai Hu
- The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA
| | | | - Glendon J. Parker
- University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
| | - James Segars
- Johns Hopkins University Medical Center, Baltimore, MD 21218, USA
| | - Ayman Al-Hendy
- The University of Illinois College of Medicine, Chicago, IL 60612, USA
| | - John I. Risinger
- Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI 48824, USA
| | - Neil T. Phippen
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Yovanni Casablanca
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
| | - Kathleen M. Darcy
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Dr., Suite 100, Bethesda, MD 20817, USA
| | - G. Larry Maxwell
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Thomas P. Conrads
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,The John P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA,Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Timothy D. O'Connor
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA,Program in Personalize and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA,Marlene and Stewart Greenebaum Comprehensive Cancer, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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25
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Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia. Blood Adv 2021; 5:4992-5001. [PMID: 34619758 PMCID: PMC9153027 DOI: 10.1182/bloodadvances.2021004735] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 08/23/2021] [Indexed: 11/20/2022] Open
Abstract
Cytogenetic lesions in pediatric AML differ by race-ethnicity including higher rates of specific poor prognosis lesions among Black children. Racial-ethnic minorities experience worse outcomes in pediatric AML regardless of genetic disease features. Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared with White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML. Compared with White non-Hispanic patients, t(8;21) AML was more prevalent among Black (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.28-3.74) and Hispanic patients (OR, 1.74; 95% CI, 1.05-2.83). The poor prognosis KMT2A rearrangement t(6;11)(q27;q23) was more prevalent among Black patients (OR, 6.12; 95% CI, 1.81-21.59). Among those with KMT2Ar AML, Black race was associated with inferior event-free survival (EFS) (hazard ratio [HR], 2.31; 95% CI, 1.41-3.79) and overall survival (OS) (HR, 2.54; 1.43-4.51). Hispanic patients with KMT2Ar AML also had inferior EFS (HR, 2.20; 95% CI, 1.27-3.80) and OS (HR, 2.07; 95% CI, 1.09-3.93). Similarly, among patients with t(8;21) or inv(16) AML (ie, core-binding factor [CBF] AML), Black patients had inferior outcomes (EFS HR, 1.93; 95% CI, 1.14-3.28 and OS HR, 3.24; 95% CI, 1.60-6.57). This disparity was not detected among patients receiving gemtuzumab ozogamicin (GO). In conclusion, racial-ethnic disparities in survival outcomes among young people with AML are prominent and vary across cytogenetic subclasses. Future studies should explore the socioeconomic and biologic determinants of these disparities.
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de la Puente M, Ruiz-Ramírez J, Ambroa-Conde A, Xavier C, Pardo-Seco J, Álvarez-Dios J, Freire-Aradas A, Mosquera-Miguel A, Gross TE, Cheung EYY, Branicki W, Nothnagel M, Parson W, Schneider PM, Kayser M, Carracedo Á, Lareu MV, Phillips C. Development and Evaluation of the Ancestry Informative Marker Panel of the VISAGE Basic Tool. Genes (Basel) 2021; 12:1284. [PMID: 34440458 PMCID: PMC8391248 DOI: 10.3390/genes12081284] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 11/29/2022] Open
Abstract
We detail the development of the ancestry informative single nucleotide polymorphisms (SNPs) panel forming part of the VISAGE Basic Tool (BT), which combines 41 appearance predictive SNPs and 112 ancestry predictive SNPs (three SNPs shared between sets) in one massively parallel sequencing (MPS) multiplex, whereas blood-based age analysis using methylation markers is run in a parallel MPS analysis pipeline. The selection of SNPs for the BT ancestry panel focused on established forensic markers that already have a proven track record of good sequencing performance in MPS, and the overall SNP multiplex scale closely matched that of existing forensic MPS assays. SNPs were chosen to differentiate individuals from the five main continental population groups of Africa, Europe, East Asia, America, and Oceania, extended to include differentiation of individuals from South Asia. From analysis of 1000 Genomes and HGDP-CEPH samples from these six population groups, the BT ancestry panel was shown to have no classification error using the Bayes likelihood calculators of the Snipper online analysis portal. The differentiation power of the component ancestry SNPs of BT was balanced as far as possible to avoid bias in the estimation of co-ancestry proportions in individuals with admixed backgrounds. The balancing process led to very similar cumulative population-specific divergence values for Africa, Europe, America, and Oceania, with East Asia being slightly below average, and South Asia an outlier from the other groups. Comparisons were made of the African, European, and Native American estimated co-ancestry proportions in the six admixed 1000 Genomes populations, using the BT ancestry panel SNPs and 572,000 Affymetrix Human Origins array SNPs. Very similar co-ancestry proportions were observed down to a minimum value of 10%, below which, low-level co-ancestry was not always reliably detected by BT SNPs. The Snipper analysis portal provides a comprehensive population dataset for the BT ancestry panel SNPs, comprising a 520-sample standardised reference dataset; 3445 additional samples from 1000 Genomes, HGDP-CEPH, Simons Foundation and Estonian Biocentre genome diversity projects; and 167 samples of six populations from in-house genotyping of individuals from Middle East, North and East African regions complementing those of the sampling regimes of the other diversity projects.
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Affiliation(s)
- María de la Puente
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Jorge Ruiz-Ramírez
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Adrián Ambroa-Conde
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Catarina Xavier
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (W.P.)
| | - Jacobo Pardo-Seco
- Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP Group), Instituto de Investigación Sanitaria de Santiago de Compostela, 15706 Santiago de Compostela, Spain;
| | - Jose Álvarez-Dios
- Faculty of Mathematics, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain;
| | - Ana Freire-Aradas
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Ana Mosquera-Miguel
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Theresa E. Gross
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany; (T.E.G.); (E.Y.Y.C.); (P.M.S.)
- Hessisches Landeskriminalamt, 65187 Wiesbaden, Germany
| | - Elaine Y. Y. Cheung
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany; (T.E.G.); (E.Y.Y.C.); (P.M.S.)
| | - Wojciech Branicki
- Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland;
| | - Michael Nothnagel
- Cologne Center for Genomics, University of Cologne, 50823 Cologne, Germany;
- University Hospital Cologne, 50937 Cologne, Germany
| | - Walther Parson
- Institute of Legal Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.X.); (W.P.)
- Forensic Science Program, The Pennsylvania State University, University Park, State College, PA 16802, USA
| | - Peter M. Schneider
- Institute of Legal Medicine, Faculty of Medicine and University Clinic, University of Cologne, 50823 Cologne, Germany; (T.E.G.); (E.Y.Y.C.); (P.M.S.)
| | - Manfred Kayser
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, 3015 CN Rotterdam, South Holland, The Netherlands;
| | - Ángel Carracedo
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
- Fundación Pública Galega de Medicina Xenómica (FPGMX), 15706 Santiago de Compostela, Spain
| | - Maria Victoria Lareu
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
| | - Christopher Phillips
- Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (M.d.l.P.); (J.R.-R.); (A.A.-C.); (A.F.-A.); (A.M.-M.); (Á.C.); (M.V.L.)
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Suárez D, Cruz R, Torres M, Mogollón F, Moncada J, Carracedo A, Usaquén W. Ancestry analysis using autosomal SNPs in northern South America, reveals interpretation differences between an AIM panel and an identification panel. Forensic Sci Int 2021; 326:110934. [PMID: 34404021 DOI: 10.1016/j.forsciint.2021.110934] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/14/2021] [Accepted: 07/23/2021] [Indexed: 12/20/2022]
Abstract
Current human populations are studied to elucidate their ancestry composition and to obtain reference values for an array of genetic markers for forensic practice. This study compared the 79 ancestry informative markers (AIMs) panel with the SNPforID 52plex set used in forensic identification, using samples belonging to Continental Caribbean populations from Colombia with a high percentage of locals self-determined as Native American descendants. The results show a bias in the individual estimation made with the identification markers, which disregards the Native American ancestry component and overestimates the African ancestry component. Also, the analysis made with the Bayesian Classification Algorithm shows better likelihoods for individual assignment with AIMs than with SNPforID 52plex.
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Affiliation(s)
- Dayana Suárez
- Populations Genetics and Identification Group, Institute of Genetics, National University of Colombia, Bogotá, Colombia.
| | - Raquel Cruz
- CIBERER, Genomic Medicine Group, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - María Torres
- Galician Public Foundation of Genomic Medicine (SERGAS)-CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Fernanda Mogollón
- Populations Genetics and Identification Group, Institute of Genetics, National University of Colombia, Bogotá, Colombia
| | - Julie Moncada
- Populations Genetics and Identification Group, Institute of Genetics, National University of Colombia, Bogotá, Colombia
| | - Angel Carracedo
- CIBERER, Genomic Medicine Group, University of Santiago de Compostela, Santiago de Compostela, Spain; Galician Public Foundation of Genomic Medicine (SERGAS)-CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain; Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain
| | - William Usaquén
- Populations Genetics and Identification Group, Institute of Genetics, National University of Colombia, Bogotá, Colombia.
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Nussbaum RL, Slotnick RN, Risch NJ. Challenges in providing residual risks in carrier testing. Prenat Diagn 2021; 41:1049-1056. [PMID: 34057205 PMCID: PMC8453722 DOI: 10.1002/pd.5975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 01/28/2023]
Abstract
The probability an individual is a carrier for a recessive disorder despite a negative carrier test, referred to as residual risk, has been part of carrier screening for over 2 decades. Residual risks are calculated by subtracting the frequency of carriers of pathogenic variants detected by the test from the carrier frequency in a population, estimated from the incidence of the disease. Estimates of the incidence (and therefore carrier frequency) of many recessive disorders differ among different population groups and are inaccurate or unavailable for many genes on large carrier screening panels for most of the world's populations. The pathogenic variants detected by the test and their frequencies also vary across groups and over time as variants are newly discovered or reclassified, which requires today's residual carrier risks to be continually updated. Even when a residual carrier risk is derived using accurate data obtained in a particular group, it may not apply to many individuals in that group because of misattributed ancestry or unsuspected admixture. Missing or inaccurate data, the challenge of determining meaningful ancestry‐specific risks and applying them appropriately, and a lack of evidence they impact management, suggest that patients be counseled that although carrier screening may miss a small fraction of carriers, residual risks with contemporary carrier screening are well below the risk posed by invasive prenatal diagnosis, even if one member of the couple is a carrier, and that efforts to provide precise residual carrier risks are unnecessary. What's already known about this topic? What does this study add?
There has been no published discussion of the methods and uncertainties involved in the calculation of residual risk that are discussed here There has been much discussion of using ancestry in genetic testing but this review highlights the serious problems that arise in calculating and assigning ancestry‐specific residual carrier risks at specific disease loci The review questions what has not been questioned before: Is there clinical utility to providing what are mostly imprecise residual carrier risks
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Affiliation(s)
- Robert Luke Nussbaum
- Invitae Corporation and Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Robert Nathan Slotnick
- Institute for Human Genetics and Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - Neil J Risch
- Institute for Human Genetics and Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA
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29
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vonHoldt BM, Aardema ML. Updating the Bibliography of Interbreeding among Canis in North America. J Hered 2021; 111:249-262. [PMID: 32034410 DOI: 10.1093/jhered/esaa004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 02/05/2020] [Indexed: 01/29/2023] Open
Abstract
This bibliography provides a collection of references that documents the evolution of studies evidencing interbreeding among Canis species in North America. Over the past several decades, advances in biology and genomic technology greatly improved our ability to detect and characterize species interbreeding, which has significance for understanding species in a changing landscape as well as for endangered species management. This bibliography includes a discussion within each category of interbreeding, the timeline of developing evidence, and includes a review of past research conducted on experimental crosses. Research conducted in the early 20th century is rich with detailed records and photographs of hybrid offspring development and behavior. With the progression of molecular methods, studies can estimate historical demographic parameters and detect chromosomal patterns of ancestry. As these methods continue to increase in accessibility, the field will gain a deeper and richer understanding of the evolutionary history of North American Canis.
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Affiliation(s)
- Bridgett M vonHoldt
- Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ
| | - Matthew L Aardema
- Department of Biology, Montclair State University, Montclair, NJ.,Sackler Institute for Comparative Genomics, American Museum of Natural History, New York City, NY
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30
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Winburn AP, Algee-Hewitt B. Evaluating population affinity estimates in forensic anthropology: Insights from the forensic anthropology database for assessing methods accuracy (FADAMA). J Forensic Sci 2021; 66:1210-1219. [PMID: 33899936 DOI: 10.1111/1556-4029.14731] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/23/2021] [Accepted: 03/29/2021] [Indexed: 12/16/2022]
Abstract
Using a sample of anonymized U.S. forensic anthropology cases (n = 251) from the FADAMA database, we assess the degree of concordance between decedents' social identifiers and anthropologists' continental-based classifications. We report high success rates (>90%) that generally support previous findings, yet we acknowledge the limitations of assessing "ancestry" accuracy based on resolved cases and draw attention to situations in which our methods fail. For example, forensic anthropologists achieve just 20% accuracy when classifying individuals as "other" or "mixed"-problematic categories that we argue should be rejected. Leveraging our findings, we ask: what are we really estimating when we perform a skeletal assessment of "ancestry" in the US context? We argue that the "ancestry estimates" historically and routinely produced in forensic anthropology instead give information on population affinity: a measure of how similar a given case is to one among several socially relevant groups of interest. Distancing forensic anthropology from genetics and other disciplines that estimate ancestry, the approach of population affinity assesses similarities to both social and biological groupings, potentially at a fine-grained level, attempting to account for the complex histories, shared biologies, and wide ranges of diversity that characterize our communities and our casework. Population affinity is a flexible and inclusive approach that more accurately describes current forensic anthropological analyses of human variation. Going forward, we must acknowledge and build on the contributions of previous scholars as we work together toward our shared goal of theoretically grounded analyses of human variation that accurately and equitably serve all casework decedents.
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Affiliation(s)
- Allysha P Winburn
- Department of Anthropology, University of West Florida, Pensacola, FL, USA
| | - Bridget Algee-Hewitt
- Center for Comparative Studies in Race and Ethnicity, Stanford University, Stanford, CA, USA
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31
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Miranda-Lora AL, Vilchis-Gil J, Juárez-Comboni DB, Cruz M, Klünder-Klünder M. A Genetic Risk Score Improves the Prediction of Type 2 Diabetes Mellitus in Mexican Youths but Has Lower Predictive Utility Compared With Non-Genetic Factors. Front Endocrinol (Lausanne) 2021; 12:647864. [PMID: 33776940 PMCID: PMC7994893 DOI: 10.3389/fendo.2021.647864] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 02/18/2021] [Indexed: 01/07/2023] Open
Abstract
Background Type 2 diabetes (T2D) is a multifactorial disease caused by a complex interplay between environmental risk factors and genetic predisposition. To date, a total of 10 single nucleotide polymorphism (SNPs) have been associated with pediatric-onset T2D in Mexicans, with a small individual effect size. A genetic risk score (GRS) that combines these SNPs could serve as a predictor of the risk for pediatric-onset T2D. Objective To assess the clinical utility of a GRS that combines 10 SNPs to improve risk prediction of pediatric-onset T2D in Mexicans. Methods This case-control study included 97 individuals with pediatric-onset T2D and 84 controls below 18 years old without T2D. Information regarding family history of T2D, demographics, perinatal risk factors, anthropometric measurements, biochemical variables, lifestyle, and fitness scores were then obtained. Moreover, 10 single nucleotide polymorphisms (SNPs) previously associated with pediatric-onset T2D in Mexicans were genotyped. The GRS was calculated by summing the 10 risk alleles. Pediatric-onset T2D risk variance was assessed using multivariable logistic regression models and the area under the receiver operating characteristic curve (AUC). Results The body mass index Z-score (Z-BMI) [odds ratio (OR) = 1.7; p = 0.009] and maternal history of T2D (OR = 7.1; p < 0.001) were found to be independently associated with pediatric-onset T2D. No association with other clinical risk factors was observed. The GRS also showed a significant association with pediatric-onset T2D (OR = 1.3 per risk allele; p = 0.006). The GRS, clinical risk factors, and GRS plus clinical risk factors had an AUC of 0.66 (95% CI 0.56-0.75), 0.72 (95% CI 0.62-0.81), and 0.78 (95% CI 0.70-0.87), respectively (p < 0.01). Conclusion The GRS based on 10 SNPs was associated with pediatric-onset T2D in Mexicans and improved its prediction with modest significance. However, clinical factors, such the Z-BMI and family history of T2D, continue to have the highest predictive utility in this population.
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Affiliation(s)
- América Liliana Miranda-Lora
- Epidemiological Research Unit in Endocrinology and Nutrition, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | - Jenny Vilchis-Gil
- Epidemiological Research Unit in Endocrinology and Nutrition, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | | | - Miguel Cruz
- Medical Research Unit in Biochemistry, Hospital de Especialidades Centro Médico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Miguel Klünder-Klünder
- Research Subdirectorate, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
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Pardo-Seco J, Gómez-Carballa A, Bello X, Martinón-Torres F, Salas A. Pitfalls of barcodes in the study of worldwide SARS-CoV-2 variation and phylodynamics. Zool Res 2021; 42:87-93. [PMID: 33410308 PMCID: PMC7840454 DOI: 10.24272/j.issn.2095-8137.2020.364] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks. We show that purely mathematical procedures for site selection should be supervised by known phylogeny (i) to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties, and (ii) to avoid phylogenetic redundancy. We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites (as a proxy for phylogenetic-based criteria). This procedure demonstrates that, for short barcodes (e.g., 11 sites), there are thousands of informative site combinations that improve previous proposals. We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny, such that most representative genomes in these ancestral nodes are no longer in circulation. Consequently, coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.
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Affiliation(s)
- Jacobo Pardo-Seco
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain.,Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Alberto Gómez-Carballa
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain.,Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Xabier Bello
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain.,Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Federico Martinón-Torres
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain.,Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia 15706, Spain
| | - Antonio Salas
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain.,Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain. E-mail:
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Pardo-Seco J, Gómez-Carballa A, Bello X, Martinón-Torres F, Salas A. Pitfalls of barcodes in the study of worldwide SARS-CoV-2 variation and phylodynamics. Zool Res 2021. [PMID: 33410308 DOI: 10.24272/j.issn.2095-8137.2020.364:1-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023] Open
Abstract
Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks. We show that purely mathematical procedures for site selection should be supervised by known phylogeny (i) to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties, and (ii) to avoid phylogenetic redundancy. We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites (as a proxy for phylogenetic-based criteria). This procedure demonstrates that, for short barcodes (e.g., 11 sites), there are thousands of informative site combinations that improve previous proposals. We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny, such that most representative genomes in these ancestral nodes are no longer in circulation. Consequently, coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.
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Affiliation(s)
- Jacobo Pardo-Seco
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Alberto Gómez-Carballa
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Xabier Bello
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
| | - Federico Martinón-Torres
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain
- Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia 15706, Spain
| | - Antonio Salas
- Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia 15706, Spain
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Galicia 15706, Spain. E-mail:
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Gutiérrez-Franco J, Ayón-Pérez MF, Durán-Avelar MDJ, Vibanco-Pérez N, Sánchez-Jasso DE, Bañuelos-Aguayo DG, Sánchez-Meza J, Pimentel-Gutiérrez HJ, Zambrano-Zaragoza JF, Agraz-Cibrián JM, Vázquez-Reyes A. High frequency of the risk allele of rs4132601 and rs11978267 from the IKZF1 gene in indigenous Mexican population. Mol Genet Genomic Med 2021; 9:e1589. [PMID: 33452870 PMCID: PMC8077075 DOI: 10.1002/mgg3.1589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/08/2020] [Accepted: 12/15/2020] [Indexed: 01/04/2023] Open
Abstract
Background IKZF1 is a relevant gene associated with the pathogenesis of acute lymphoblastic leukemia, and the rs4132601 (T>G) and rs11978267 (A>G) polymorphisms have been associated with the development of this disease in several populations. The aim of this study was to determine the allelic and genotypic frequencies of the rs4132601 and rs11978267 polymorphisms in two indigenous Mexican groups (Cora and Huichol) and Mestizo populations from Nayarit, Mexico, and compare them with the frequencies of both polymorphisms in other populations of the world. Methods One hundred, 116, and 100 subjects from the Mestizo, Huichol, and Cora populations, respectively, all of them residents of the state of Nayarit, Mexico, were analyzed. The frequencies of rs4132601 and rs11978267 were determined by allelic discrimination using TaqMan assays. Results The allelic frequencies of rs4132601 were as follows: Mestizo group T = 0.74, G = 0.26; Cora T = 0.745, G = 0.255; and Huichol T = 0.47, G = 0.53. In the case of the rs11978267 polymorphism, the allelic frequencies were Mestizo A = 0.745, G = 0.255; Cora A = 0.735, G = 0.265; and Huichol A = 0.457, G = 0.543. For each population, both polymorphisms were in Hardy–Weinberg equilibrium. Conclusion The Huichol population from Nayarit presented the highest frequencies of the risk allele reported to date in the whole world for both rs4132601 and rs11978267 polymorphisms.
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Affiliation(s)
- Jorge Gutiérrez-Franco
- Laboratorio de Inmunología, Unidad Académica de Ciencias Químico-Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Miriam Fabiola Ayón-Pérez
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Ma de Jesús Durán-Avelar
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Norberto Vibanco-Pérez
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Diego Eduardo Sánchez-Jasso
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Dulce Guadalupe Bañuelos-Aguayo
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Jaime Sánchez-Meza
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | | | - José Francisco Zambrano-Zaragoza
- Laboratorio de Inmunología, Unidad Académica de Ciencias Químico-Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Juan Manuel Agraz-Cibrián
- Laboratorio de Inmunología, Unidad Académica de Ciencias Químico-Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
| | - Alejandro Vázquez-Reyes
- Laboratorios de Investigación en Biología Molecular e Inmunología, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México
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Debortoli G, de Araujo GS, Fortes-Lima C, Parra EJ, Suarez-Kurtz G. Identification of ancestry proportions in admixed groups across the Americas using clinical pharmacogenomic SNP panels. Sci Rep 2021; 11:1007. [PMID: 33441860 PMCID: PMC7806998 DOI: 10.1038/s41598-020-80389-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 12/14/2020] [Indexed: 11/09/2022] Open
Abstract
We evaluated the performance of three PGx panels to estimate biogeographical ancestry: the DMET panel, and the VIP and Preemptive PGx panels described in the literature. Our analysis indicate that the three panels capture quite well the individual variation in admixture proportions observed in recently admixed populations throughout the Americas, with the Preemptive PGx and DMET panels performing better than the VIP panel. We show that these panels provide reliable information about biogeographic ancestry and can be used to guide the implementation of PGx clinical decision-support (CDS) tools. We also report that using these panels it is possible to control for the effects of population stratification in association studies in recently admixed populations, as exemplified with a warfarin dosing GWA study in a sample from Brazil.
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Affiliation(s)
- Guilherme Debortoli
- Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada
| | | | - Cesar Fortes-Lima
- Sub-Department of Human Evolution, Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden
| | - Esteban J Parra
- Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
| | - Guilherme Suarez-Kurtz
- Instituto Nacional de Câncer and Rede Nacional de Farmacogenética, Rio de Janeiro, Brazil.
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36
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Parfenchyk MS, Kotava SA. The Theoretical Framework for the Panels of DNA Markers Formation in the Forensic Determination of an Individual Ancestral Origin. RUSS J GENET+ 2021. [DOI: 10.1134/s1022795421010105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Colistro V, Mut P, Hidalgo PC, Carracedo A, Quintela I, Rojas-Martínez A, Sans M. Differential admixture in Latin American populations and its impact on the study of colorectal cancer. Genet Mol Biol 2020; 43:e20200143. [PMID: 33306774 PMCID: PMC7783724 DOI: 10.1590/1678-4685-gmb-2020-0143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 09/14/2020] [Indexed: 11/22/2022] Open
Abstract
Genome-wide association studies focused on searching genes responsible for
several diseases. Admixture mapping studies proposed a more efficient
alternative capable of detecting polymorphisms contributing with a small effect
on the disease risk. This method focuses on the higher values of linkage
disequilibrium in admixed populations. To test this, we analyzed 10 genomic
regions previously defined as related with colorectal cancer among nine
populations and studied the variation pattern of haplotypic structures and
heterozygosity values on seven categories of SNPs. Both analyses showed
differences among chromosomal regions and studied populations. Admixed
Latin-American samples generally show intermediate values. Heterozygosity of the
SNPs grouped in categories varies more in each gene than in each population.
African related populations have more blocks per chromosomal region, coherently
with their antiquity. In sum, some similarities were found among Latin American
populations, but each chromosomal region showed a particular behavior, despite
the fact that the study refers to genes and regions related with one particular
complex disease. This study strongly suggests the necessity of developing
statistical methods to deal with di- or tri-hybrid populations, as well as to
carefully analyze the different historic and demographic scenarios, and the
different characteristics of particular chromosomal regions and evolutionary
forces.
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Affiliation(s)
- Valentina Colistro
- Universidad de la República, Facultad de Medicina, Departamento de Métodos Cuantitativos, Montevideo, Uruguay
| | - Patricia Mut
- Universidad de la República, Facultad de Humanidades y Ciencias de la Educación, Departamento de Antropología Biológica, Montevideo, Uruguay
| | - Pedro C Hidalgo
- Universidad de la República, Centro Universitario de Tacuarembó, Polo de Desarrollo Universitario Diversidad Genética Humana, Tacuarembó, Uruguay
| | - Angel Carracedo
- Universidad de Santiago de Compostela, Centro Nacional de Genotipado (CEGEN), Spain.,Universidade de Santiago de Compostela, CIBER de Enfermedades Raras (CIBERER)-Instituto de Salud Carlos III, Grupo de Medicina Xenómica, Santiago de Compostela, Spain
| | - Inés Quintela
- Universidad de Santiago de Compostela, Centro Nacional de Genotipado (CEGEN), Spain
| | | | - Mónica Sans
- Universidad de la República, Facultad de Humanidades y Ciencias de la Educación, Departamento de Antropología Biológica, Montevideo, Uruguay
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Torres-Valadez R, Ramos-Lopez O, Frías Delgadillo KJ, Flores-García A, Rojas Carrillo E, Aguiar-García P, Bernal Pérez JA, Martinez-Lopez E, Martínez JA, Zepeda-Carrillo EA. Impact of APOE Alleles-by-Diet Interactions on Glycemic and Lipid Features- A Cross-Sectional Study of a Cohort of Type 2 Diabetes Patients from Western Mexico: Implications for Personalized Medicine. PHARMACOGENOMICS & PERSONALIZED MEDICINE 2020; 13:655-663. [PMID: 33273843 PMCID: PMC7705254 DOI: 10.2147/pgpm.s277952] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 10/23/2020] [Indexed: 12/13/2022]
Abstract
Purpose To analyze clinically relevant interactions between the apolipoprotein E (APOE) ε2, ε3 and ε4 alleles and nutritional factors on glycemic control and lipid levels in a cohort of type 2 diabetes (T2D) patients from western Mexico. Patients and Methods In this cross-sectional study of the cohort of T2D patients, a total of 224 individuals were selected for interaction studies. Clinical and anthropometric data were obtained from pre-designed medical records. Dietary intake was assessed by validated three-day food consumption records. Biochemical measurements were determined by automated methods. APOE genotyping was performed by a real-time allelic discrimination assay. Gene–diet interactions were tested by corrected multiple linear regression analyses, which were adjusted by potential confounding factors such as age, sex, energy intake, BMI and anti-hyperglycemic therapy (Metformin, Glibenclamide or Insulin), and years with T2D. Results Seventy-six percent of patients with T2D were on Metformin therapy. The frequencies of the APOE alleles were ε2 (5.8%), ε3 (74.1%) and ε4 (20.1%). After statistical settings, significant APOE alleles-by-diet interactions in relation to the metabolic profile were found. Interestingly, higher blood levels of total cholesterol (p int. = 0.016), non-HDL-c (p int. = 0.024), and LDL-c (p int. = 0.030) were found only in carriers of the APOE ε2 allele with a low consumption of MUFA. In contrast, carriers of the APOE ε4 allele with a high ω-6:ω-3 PUFA ratio in the diet had higher %HbA1c blood concentrations (p int. = 0.035). Conclusion This study suggests a differential metabolic impact of APOE alleles on lipid/glycemic phenotypes depending on the dietary intake, with important potential implications in the personalized medicine and nutritional management of patients with type 2 diabetes mellitus.
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Affiliation(s)
- Rafael Torres-Valadez
- Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico.,Integral Health Academic Unit, Autonomous University of Nayarit, Tepic, Nayarit, Mexico
| | - Omar Ramos-Lopez
- Faculty of Medicine and Psychology, Autonomous University of Baja California, Tijuana, Baja California, Mexico
| | - Kevin J Frías Delgadillo
- Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico
| | - Aurelio Flores-García
- Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico
| | - Esaú Rojas Carrillo
- Family Medicine Unit No. 24 "Ignacio García Tellez", Mexican Social Security Institute, Tepic, Nayarit, Mexico
| | - Pedro Aguiar-García
- Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico
| | - J Antonio Bernal Pérez
- Family Medicine Unit No. 24 "Ignacio García Tellez", Mexican Social Security Institute, Tepic, Nayarit, Mexico
| | - Erika Martinez-Lopez
- Institute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular and Genomic Biology, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - J Alfredo Martínez
- Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Madrid, Spain.,CIBERobn, Fisiopatología De La Obesidad y La Nutrición, Carlos III Health Institute, Madrid, Spain
| | - Eloy A Zepeda-Carrillo
- Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico.,Tepic Civil Hospital "Dr. Antonio González Guevara", Health Services in Nayarit, Tepic, Nayarit, Mexico
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Pena SDJ, Santos FR, Tarazona-Santos E. Genetic admixture in Brazil. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS 2020; 184:928-938. [PMID: 33205899 DOI: 10.1002/ajmg.c.31853] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/23/2020] [Accepted: 11/02/2020] [Indexed: 12/21/2022]
Abstract
We review studies from our laboratories using different molecular tools to characterize the Amerindian, European and African ancestry of Brazilians. Initially we used uniparental DNA markers to investigate the contribution of distinct Y chromosome and mitochondrial DNA lineages to present-day populations. High levels of genetic admixture and strong directional mating between European males and Amerindian and African females were unraveled. We next analyzed different types of biparental autosomal polymorphisms. Especially useful was a set of 40 insertion-deletion polymorphisms (indels) that when studied worldwide proved exquisitely sensitive in discriminating between Amerindians, Europeans and Sub-Saharan Africans. When applied to the study of Brazilians these markers confirmed extensive genomic admixture. We then studied ancestry differences in different regions by statistically controlling them to eliminate color considerations. The European ancestry was predominant in all regions studied, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of 6 million Europeans to Brazil in the 19th and 20th centuries is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. Brazilians should be assessed individually, as 210 million human beings, and not as members of specific regions or color groups.
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Affiliation(s)
- Sergio D J Pena
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Fabrício R Santos
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Eduardo Tarazona-Santos
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Instituto de Estudos Avançados Transdisciplinares, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima, Peru
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40
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Xavier C, de la Puente M, Mosquera-Miguel A, Freire-Aradas A, Kalamara V, Vidaki A, E. Gross T, Revoir A, Pośpiech E, Kartasińska E, Spólnicka M, Branicki W, E. Ames C, M. Schneider P, Hohoff C, Kayser M, Phillips C, Parson W. Development and validation of the VISAGE AmpliSeq basic tool to predict appearance and ancestry from DNA. Forensic Sci Int Genet 2020; 48:102336. [DOI: 10.1016/j.fsigen.2020.102336] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 05/28/2020] [Accepted: 06/08/2020] [Indexed: 12/19/2022]
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41
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Pereira V, Santangelo R, Børsting C, Tvedebrink T, Almeida APF, Carvalho EF, Morling N, Gusmão L. Evaluation of the Precision of Ancestry Inferences in South American Admixed Populations. Front Genet 2020; 11:966. [PMID: 32973885 PMCID: PMC7472784 DOI: 10.3389/fgene.2020.00966] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/31/2020] [Indexed: 11/13/2022] Open
Abstract
Ancestry informative markers (AIMs) are used in forensic genetics to infer biogeographical ancestry (BGA) of individuals and may also have a prominent role in future police and identification investigations. In the last few years, many studies have been published reporting new AIM sets. These sets include markers (usually around 100 or less) selected with different purposes and different population resolutions. Regardless of the ability of these sets to separate populations from different continents or regions, the uncertainty associated with the estimates provided by these panels and their capacity to accurately report the different ancestral contributions in individuals of admixed populations has rarely been investigated. This issue is addressed in this study by evaluating different AIM sets. Ancestry inference was carried out in admixed South American populations, both at population and individual levels. The results of ancestry inferences using AIM sets with different numbers of markers among admixed reference populations were compared. To evaluate the performance of the different ancestry panels at the individual level, expected and observed estimates among families and their offspring were compared, considering that (1) the apportionment of ancestry in the offspring should be closer to the average ancestry of the parents, and (2) full siblings should present similar ancestry values. The results obtained illustrate the importance of having a good balance/compromise between not only the number of markers and their ability to differentiate ancestral populations, but also a balanced differentiation among reference groups, to obtain more precise values of genetic ancestry. This work also highlights the importance of estimating errors associated with the use of a limited number of markers. We demonstrate that although these errors have a moderate effect at the population level, they may have an important impact at the individual level. Considering that many AIM-sets are being described for inferences at the individual level and not at the population level, e.g., in association studies or the determination of a suspect's BGA, the results of this work point to the need of a more careful evaluation of the uncertainty associated with the ancestry estimates in admixed populations, when small AIM-sets are used.
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Affiliation(s)
- Vania Pereira
- Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Roberta Santangelo
- Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Claus Børsting
- Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Torben Tvedebrink
- Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark
| | - Ana Paula F Almeida
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Elizeu F Carvalho
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Niels Morling
- Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Leonor Gusmão
- DNA Diagnostic Laboratory, State University of Rio de Janeiro, Rio de Janeiro, Brazil.,Instituto de Investigação e Inovação em Saúde, i3S, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
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42
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Rotroff DM. A Bioinformatics Crash Course for Interpreting Genomics Data. Chest 2020; 158:S113-S123. [PMID: 32658646 PMCID: PMC8176646 DOI: 10.1016/j.chest.2020.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 11/11/2019] [Accepted: 03/09/2020] [Indexed: 10/23/2022] Open
Abstract
Reductions in genotyping costs and improvements in computational power have made conducting genome-wide association studies (GWAS) standard practice for many complex diseases. GWAS is the assessment of genetic variants across the genome of many individuals to determine which, if any, genetic variants are associated with a specific trait. As with any analysis, there are evolving best practices that should be followed to ensure scientific rigor and reliability in the conclusions. This article presents a brief summary for many of the key bioinformatics considerations when either planning or evaluating GWAS. This review is meant to serve as a guide to those without deep expertise in bioinformatics and GWAS and give them tools to critically evaluate this popular approach to investigating complex diseases. In addition, a checklist is provided that can be used by investigators to evaluate whether a GWAS has appropriately accounted for the many potential sources of bias and generally followed current best practices.
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Affiliation(s)
- Daniel M Rotroff
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
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43
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Shoag JM, Barredo JC, Lossos IS, Pinheiro PS. Acute lymphoblastic leukemia mortality in Hispanic Americans. Leuk Lymphoma 2020; 61:2674-2681. [DOI: 10.1080/10428194.2020.1779260] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Jamie M. Shoag
- Department of Pediatric, Hematology and Oncology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Julio C. Barredo
- Department of Pediatric, Hematology and Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Izidore S. Lossos
- Department of Medicine, Hematology and Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Paulo S. Pinheiro
- Department of Public Health Sciences, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
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44
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Karnes JH, Wiener HW, Schwantes-An TH, Natarajan B, Sweatt AJ, Chaturvedi A, Arora A, Batai K, Nair V, Steiner HE, Giles JB, Yu J, Hosseini M, Pauciulo MW, Lutz KA, Coleman AW, Feldman J, Vanderpool R, Tang H, Garcia JGN, Yuan JXJ, Kittles R, de Jesus Perez V, Zamanian RT, Rischard F, Tiwari HK, Nichols WC, Benza RL, Desai AA. Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 201:1407-1415. [PMID: 31916850 PMCID: PMC7258627 DOI: 10.1164/rccm.201907-1447oc] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis.Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50-0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034).Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.
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Affiliation(s)
| | - Howard W. Wiener
- Department of Biostatistics, University of Alabama–Birmingham, Birmingham, Alabama
| | | | - Balaji Natarajan
- Department of Cardiology, University of California Riverside School of Medicine, Riverside, California
| | - Andrew J. Sweatt
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, California,Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California
| | | | - Amit Arora
- Department of Epidemiology and Biostatistics
| | | | - Vineet Nair
- Department of Medicine, University of Arizona, Tucson, Arizona
| | | | | | - Jeffrey Yu
- Department of Pharmacy Practice and Science
| | - Maryam Hosseini
- Department of Medicine, University of Arizona, Tucson, Arizona
| | - Michael W. Pauciulo
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Katie A. Lutz
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Anna W. Coleman
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | | | - Haiyang Tang
- Department of Medicine, University of Arizona, Tucson, Arizona
| | | | - Jason X.-J. Yuan
- Department of Medicine, University of California–San Diego, La Jolla, California; and
| | - Rick Kittles
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Vinicio de Jesus Perez
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, California,Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California
| | - Roham T. Zamanian
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, California,Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California
| | - Franz Rischard
- Department of Medicine, University of Arizona, Tucson, Arizona
| | - Hemant K. Tiwari
- Department of Biostatistics, University of Alabama–Birmingham, Birmingham, Alabama
| | - William C. Nichols
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Ankit A. Desai
- Department of Medicine, Indiana University, Indianapolis, Indiana
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45
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Shieh Y, Fejerman L, Lott PC, Marker K, Sawyer SD, Hu D, Huntsman S, Torres J, Echeverry M, Bohórquez ME, Martínez-Chéquer JC, Polanco-Echeverry G, Estrada-Flórez AP, Haiman CA, John EM, Kushi LH, Torres-Mejía G, Vidaurre T, Weitzel JN, Zambrano SC, Carvajal-Carmona LG, Ziv E, Neuhausen SL. A Polygenic Risk Score for Breast Cancer in US Latinas and Latin American Women. J Natl Cancer Inst 2020; 112:590-598. [PMID: 31553449 PMCID: PMC7301155 DOI: 10.1093/jnci/djz174] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 07/23/2019] [Accepted: 09/04/2019] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND More than 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Because most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry. METHODS We conducted a pooled case-control analysis of US Latinas and Latin American women (4658 cases and 7622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (P < 5 × 10-8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression, and assessed discrimination using an area under the receiver operating characteristic curve. We also assessed PRS performance across quartiles of Indigenous American genetic ancestry. All statistical tests were two-sided. RESULTS Of 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally statistically significant (P < .05). The PRS was associated with breast cancer risk, with an odds ratio per SD increment of 1.58 (95% confidence interval [CI = 1.52 to 1.64) and an area under the receiver operating characteristic curve of 0.63 (95% CI = 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry. CONCLUSIONS The 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.
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Affiliation(s)
- Yiwey Shieh
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Laura Fejerman
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Paul C Lott
- UC Davis Genome Center, University of California, Davis, Davis, CA
| | - Katie Marker
- School of Public Health, University of California, Berkeley; Berkeley, CA
| | | | - Donglei Hu
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Scott Huntsman
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Javier Torres
- Unidad de Investigación en Enfermedades Infecciosas, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Magdalena Echeverry
- Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia
| | - Mabel E Bohórquez
- Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia
| | | | | | - Ana P Estrada-Flórez
- UC Davis Genome Center, University of California, Davis, Davis, CA
- Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia
| | | | - Christopher A Haiman
- Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Esther M John
- Department of Medicine, Stanford University School of Medicine, Stanford, CA
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
| | - Lawrence H Kushi
- UC Davis Genome Center, University of California, Davis, Davis, CA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | | | | | - Jeffrey N Weitzel
- Division of Clinical Genetics, City of Hope National Medical Center, Duarte, CA
| | | | - Luis G Carvajal-Carmona
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA
- Population Science and Health Disparities Program, University of California Davis Comprehensive Cancer Center, Sacramento, CA
| | - Elad Ziv
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Susan L Neuhausen
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA
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46
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Developing ancestry informative marker panel for Nigeria-Cameroonian chimpanzees. J Genet 2020. [DOI: 10.1007/s12041-020-01192-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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47
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Setser CH, Planz JV, Barber RC, Phillips NR, Chakraborty R, Cross DS. Differentiation of Hispanic biogeographic ancestry with 80 ancestry informative markers. Sci Rep 2020; 10:7745. [PMID: 32385290 PMCID: PMC7210943 DOI: 10.1038/s41598-020-64245-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 04/03/2020] [Indexed: 11/09/2022] Open
Abstract
Ancestry informative single nucleotide polymorphisms (SNPs) can identify biogeographic ancestry (BGA); however, population substructure and relatively recent admixture can make differentiation difficult in heterogeneous Hispanic populations. Utilizing unrelated individuals from the Genomic Origins and Admixture in Latinos dataset (GOAL, n = 160), we designed an 80 SNP panel (Setser80) that accurately depicts BGA through STRUCTURE and PCA. We compared our Setser80 to the Seldin and Kidd panels via resampling simulations, which models data based on allele frequencies. We incorporated Admixed American 1000 Genomes populations (1000 G, n = 347), into a combined populations dataset to determine robustness. Using multinomial logistic regression (MLR), we compared the 3 panels on the combined dataset and found overall MLR classification accuracies: 93.2% Setser80, 87.9% Seldin panel, 71.4% Kidd panel. Naïve Bayesian classification had similar results on the combined dataset: 91.5% Setser80, 84.7% Seldin panel, 71.1% Kidd panel. Although Peru and Mexico were absent from panel design, we achieved high classification accuracy on the combined populations for Peru (MLR = 100%, naïve Bayes = 98%), and Mexico (MLR = 90%, naïve Bayes = 83.4%) as evidence of the portability of the Setser80. Our results indicate the Setser80 SNP panel can reliably classify BGA for individuals of presumed Hispanic origin.
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Affiliation(s)
- Casandra H Setser
- University of North Texas Health Science Center; Department of Microbiology, Immunology, and Genetics, Fort Worth, TX, USA.
| | - John V Planz
- University of North Texas Health Science Center; Department of Microbiology, Immunology, and Genetics, Fort Worth, TX, USA
| | - Robert C Barber
- University of North Texas Health Science Center; Department of Microbiology, Immunology, and Genetics, Fort Worth, TX, USA
| | - Nicole R Phillips
- University of North Texas Health Science Center; Department of Microbiology, Immunology, and Genetics, Fort Worth, TX, USA
| | - Ranajit Chakraborty
- University of North Texas Health Science Center; Department of Microbiology, Immunology, and Genetics, Fort Worth, TX, USA
| | - Deanna S Cross
- University of North Texas Health Science Center; Department of Physician Assistant Studies, Fort Worth, TX, USA
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48
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Verdugo RA, Di Genova A, Herrera L, Moraga M, Acuña M, Berríos S, Llop E, Valenzuela CY, Bustamante ML, Digman D, Symon A, Asenjo S, López P, Blanco A, Suazo J, Barozet E, Caba F, Villalón M, Alvarado S, Cáceres D, Salgado K, Portales P, Moreno-Estrada A, Gignoux CR, Sandoval K, Bustamante CD, Eng C, Huntsman S, Burchard EG, Loira N, Maass A, Cifuentes L. Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components. Biol Res 2020; 53:15. [PMID: 32299502 PMCID: PMC7161194 DOI: 10.1186/s40659-020-00284-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 04/09/2020] [Indexed: 12/30/2022] Open
Abstract
Background Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. Results A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country’s average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. Conclusions We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.
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Affiliation(s)
- Ricardo A Verdugo
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.,Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Alex Di Genova
- Mathomics, Centro de Modelamiento Matemático y Centro para la Regulación del Genoma, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
| | - Luisa Herrera
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Mauricio Moraga
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Mónica Acuña
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Soledad Berríos
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Elena Llop
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Carlos Y Valenzuela
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - M Leonor Bustamante
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.,Departamento de Psiquiatría, y Salud Mental Norte, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Dayhana Digman
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Adriana Symon
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Soledad Asenjo
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Pamela López
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - Alejandro Blanco
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
| | - José Suazo
- Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile
| | - Emmanuelle Barozet
- Departamento de Sociología, Facultad de Ciencias Sociales, Universidad de Chile, Centro de Estudios de Conflicto y Cohesión, Social, Santiago, Chile
| | - Fresia Caba
- Facultad de Ciencias de la Salud, Universidad de Tarapacá, Arica, Chile
| | - Marcelo Villalón
- Instituto de Salud Poblacional "Escuela de Salud Pública", Universidad de Chile, Santiago, Chile
| | - Sergio Alvarado
- Instituto de Salud Poblacional "Escuela de Salud Pública", Universidad de Chile, Santiago, Chile
| | - Dante Cáceres
- Instituto de Salud Poblacional "Escuela de Salud Pública", Universidad de Chile, Santiago, Chile
| | - Katherine Salgado
- Facultad de Ciencias de la Salud, Universidad de Tarapacá, Arica, Chile
| | - Pilar Portales
- Corporación Municipal de Desarrollo Social, Iquique, Chile
| | - Andrés Moreno-Estrada
- National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Guanajuato, 36821, Mexico
| | | | - Karla Sandoval
- National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Guanajuato, 36821, Mexico
| | | | - Celeste Eng
- Department of Medicine, University of California, San Francisco, CA, USA
| | - Scott Huntsman
- Department of Medicine, University of California, San Francisco, CA, USA
| | - Esteban G Burchard
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA
| | - Nicolás Loira
- Mathomics, Centro de Modelamiento Matemático y Centro para la Regulación del Genoma, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
| | - Alejandro Maass
- Mathomics, Centro de Modelamiento Matemático y Centro para la Regulación del Genoma, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile.,Departamento de Ingeniería Matemática, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile
| | - Lucía Cifuentes
- Programa de Genética Humana del ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
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Abstract
Multiple sclerosis (MS) has a strong racial and ethnic component and disproportionately affects whites of European background. Recent incidence reports suggest an increasing rate of MS among African Americans compared with whites. Despite this recent increase in MS in African Americans, Hispanics and Asians are significantly less likely to develop MS than whites of European ancestry. MS-specific mortality trends demonstrate distinctive disparities by race/ethnicity and age, suggesting that there is an unequal burden of disease. Inequalities in health along with differences in clinical characteristics that may be genetic, environmental, and social in origin may be contributing to disease variability and be suggestive of endophenotypes. The overarching goal of this review was to summarize the current understanding on the variability of disease that we observe in selected racial and ethnic populations: Hispanics and African Americans. Future challenges will be to unravel the genetic, environmental, and social determinants of the observed racial/ethnic disparities.
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Affiliation(s)
- Lilyana Amezcua
- Multiple Sclerosis Comprehensive Care Center, University of Southern California, Los Angeles, CA, USA/Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Jacob L McCauley
- John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA
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Wang LJ, Zhang CW, Su SC, Chen HIH, Chiu YC, Lai Z, Bouamar H, Ramirez AG, Cigarroa FG, Sun LZ, Chen Y. An ancestry informative marker panel design for individual ancestry estimation of Hispanic population using whole exome sequencing data. BMC Genomics 2019; 20:1007. [PMID: 31888480 PMCID: PMC6936141 DOI: 10.1186/s12864-019-6333-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background Europeans and American Indians were major genetic ancestry of Hispanics in the U.S. These ancestral groups have markedly different incidence rates and outcomes in many types of cancers. Therefore, the genetic admixture may cause biased genetic association study with cancer susceptibility variants specifically in Hispanics. For example, the incidence rate of liver cancer has been shown with substantial disparity between Hispanic, Asian and non-Hispanic white populations. Currently, ancestry informative marker (AIM) panels have been widely utilized with up to a few hundred ancestry-informative single nucleotide polymorphisms (SNPs) to infer ancestry admixture. Notably, current available AIMs are predominantly located in intron and intergenic regions, while the whole exome sequencing (WES) protocols commonly used in translational research and clinical practice do not cover these markers. Thus, it remains challenging to accurately determine a patient’s admixture proportion without additional DNA testing. Results In this study we designed an unique AIM panel that infers 3-way genetic admixture from three distinct and selective continental populations (African (AFR), European (EUR), and East Asian (EAS)) within evolutionarily conserved exonic regions. Initially, about 1 million exonic SNPs from selective three populations in the 1000 Genomes Project were trimmed by their linkage disequilibrium (LD), restricted to biallelic variants, and finally we optimized to an AIM panel with 250 SNP markers, or the UT-AIM250 panel, using their ancestral informativeness statistics. Comparing to published AIM panels, UT-AIM250 performed better accuracy when we tested with three ancestral populations (accuracy: 0.995 ± 0.012 for AFR, 0.997 ± 0.007 for EUR, and 0.994 ± 0.012 for EAS). We further demonstrated the performance of the UT-AIM250 panel to admixed American (AMR) samples of the 1000 Genomes Project and obtained similar results (AFR, 0.085 ± 0.098; EUR, 0.665 ± 0.182; and EAS, 0.250 ± 0.205) to previously published AIM panels (Phillips-AIM34: AFR, 0.096 ± 0.127, EUR, 0.575 ± 0.290, and EAS, 0.330 ± 0.315; Wei-AIM278: AFR, 0.070 ± 0.096, EUR, 0.537 ± 0.267, and EAS, 0.393 ± 0.300). Subsequently, we applied the UT-AIM250 panel to a clinical dataset of 26 self-reported Hispanic patients in South Texas with hepatocellular carcinoma (HCC). We estimated the admixture proportions using WES data of adjacent non-cancer liver tissues (AFR, 0.065 ± 0.043; EUR, 0.594 ± 0.150; and EAS, 0.341 ± 0.160). Similar admixture proportions were identified from corresponding tumor tissues. In addition, we estimated admixture proportions of The Cancer Genome Atlas (TCGA) collection of hepatocellular carcinoma (TCGA-LIHC) samples (376 patients) using the UT-AIM250 panel. The panel obtained consistent admixture proportions from tumor and matched normal tissues, identified 3 possible incorrectly reported race/ethnicity, and/or provided race/ethnicity determination if necessary. Conclusions Here we demonstrated the feasibility of using evolutionarily conserved exonic regions to infer admixture proportions and provided a robust and reliable control for sample collection or patient stratification for genetic analysis. R implementation of UT-AIM250 is available at https://github.com/chenlabgccri/UT-AIM250.
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Affiliation(s)
- Li-Ju Wang
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Catherine W Zhang
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Sophia C Su
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Hung-I H Chen
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Yu-Chiao Chiu
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Zhao Lai
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.,Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Hakim Bouamar
- Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Amelie G Ramirez
- Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.,Institute for Health Promotion Research, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Francisco G Cigarroa
- Department of Surgery, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Lu-Zhe Sun
- Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, 78229, USA
| | - Yidong Chen
- Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, 78229, USA. .,Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.
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