Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jul 19, 2022; 12(7): 904-914
Published online Jul 19, 2022. doi: 10.5498/wjp.v12.i7.904
ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population
Xin-Wei Li, Ming-Yuan Zhang, Zhi-Jun Li, Li-Zhe Ai, Meng-Di Jin, Ning-Ning Jia, Meng-Tong Xie, Yu-Qing Yang, Wei-Zhen Li, Lin Dong, Qiong Yu
Xin-Wei Li, Zhi-Jun Li, Li-Zhe Ai, Meng-Di Jin, Ning-Ning Jia, Meng-Tong Xie, Yu-Qing Yang, Wei-Zhen Li, Lin Dong, Qiong Yu, Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
Ming-Yuan Zhang, Department of Endemic Diseases and Parasitic Diseases Prevention, Yantai Center for Disease Control and Prevention, Yantai 264003, Shandong Province, China
Author contributions: Li XW and Zhang MY performed the majority of experiments and wrote the manuscript; Li ZJ and Ai LZ provided advices to the manuscript correction; Jin MD served as scientific advisor and participated in the collection of human material; Jia NN was involved in analytical tools; Xie MT, Yang YQ, Li WZ and Dong L participated in the collection of the human material; Yu Q designed the study and is the guarantor; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81673253; and Jilin Provincial Ministry of Education S&T Project, No. JJKH20190091KJ.
Institutional review board statement: The study was approved by the Ethics Committee of the School of Public Health of Jilin University (No. 2014-03-11).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author Qiong Yu upon reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiong Yu, MD, PhD, Professor, Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No. 1163 Xinmin Street, Chaoyang District, Changchun 130021, Jilin Province, China. yuqiong@jlu.edu.cn
Received: January 28, 2022
Peer-review started: January 28, 2022
First decision: April 18, 2022
Revised: May 2, 2022
Accepted: June 17, 2022
Article in press: June 17, 2022
Published online: July 19, 2022
Processing time: 171 Days and 17.6 Hours
Abstract
BACKGROUND

Schizophrenia (SCZ) is a complex disease which can be affected by both genetic and environmental factors. Prenatal famine exposure may cause changes in DNA methylation levels of genes. Meanwhile, maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ. DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ, and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine.

AIM

To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.

METHODS

A total of 954 Han Chinese from Northeast China were recruited, including 443 patients with SCZ and 511 healthy controls. The participants were further divided into famine (born in 1960-1962) and non-famine (born in 1963-1965) groups to investigate the effect of prenatal famine exposure. Four single-nucleotide polymorphisms (SNPs) selected according to the relevant literature were genotyped, namely, rs11917047 in PTPRG, rs2239681 in IGF2, rs3842756 in INSIGF, and rs61955196 in ABCB9. DNA were extracted from peripheral blood samples, and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique. The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine, and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction (GMDR) software.

RESULTS

Based on the sequencing data, genotype distributions and allele frequencies of the four selected SNPs were determined. All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium (P > 0.05). Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model [odds ratio (OR): 1.22; 95% confidence interval (CI): 1.01-1.48; P = 0.040]. We also found that the rs61955196 allele was related with an enhanced risk of SCZ (G>C, OR: 1.22; 95%CI: 1.01-1.47; P = 0.042). However, no associations were observed between rs11917047, rs2239681, or rs3842756 and SCZ risk. Under the optimal genetic model, no significant association of famine with the four SNPs was seen. Though the gene–gene interactions between rs2239681 and rs61955196 were found in GMDR analysis, none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.

CONCLUSION

Our study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese, providing insight into genetic effects on SCZ.

Keywords: Schizophrenia; Prenatal famine; rs61955196; DNA methylation; ABCB9 polymorphism

Core Tip: Prenatal famine exposure may cause changes in DNA methylation levels of genes, while maternal nutrition is a pivotal environmental factor for schizophrenia (SCZ). To analyze the association between prenatal famine exposure and SCZ risk, we recruited 443 SCZ patients and 511 healthy controls with four single-nucleotide polymorphisms genotyped, which were previously identified as DNA methylation quantitative trait loci. Our study observed significant differences in rs61955196 genotype distribution and allele frequency between SCZ patients and healthy controls for the first time, suggesting that rs61955196 in ABCB9 was associated with SCZ susceptibility among the Northeast Han Chinese population.