Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5050-5059
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5050
Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity
Frederik Trier Moller, Lina Knudsen, Marcus Harbord, Jack Satsangi, Hannah Gordon, Lene Christiansen, Kaare Christensen, Tine Jess, Vibeke Andersen
Frederik Trier Moller, Lina Knudsen, Vibeke Andersen, Research Unit for Molecular Diagnostics, Hospital of Southern Jutland, 6200 Aabenraa, Denmark
Frederik Trier Moller, Lina Knudsen, Lene Christiansen, Kaare Christensen, Vibeke Andersen, Institute of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
Frederik Trier Moller, Tine Jess, Division of Epidemiology and Disease Surveillance, Statens Serum Institut, 2300 Copenhagen, Denmark
Marcus Harbord, Hannah Gordon, Department of Gastroenterology, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom
Jack Satsangi, Centre for Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
Lene Christiansen, Kaare Christensen, Danish Ageing Research Centre, Institute of Public Health, University of Southern Denmark, 5000 Odense, Denmark
Tine Jess, Department of Clinical Medicine, University of Aalborg, 9000 Aalborg, Denmark
Author contributions: Moller FT, Knudsen L, Harbord M, Satsangi J, Gordon H, Christiansen L, Christensen K, Jess T and Andersen V concepted and designed the study; Moller FT performed generation and analysis of data; Moller FT, Jess T and Andersen V interpreted the data; Moller FT drafted the manuscript; Moller FT, Andersen V, Jess T, Knudsen L, Harbord M, Satsangi J, Gordon H, Christiansen L and Christensen K performed critical revision and approved of the final version of the manuscript.
Supported by Lundbeck foundation, Region of Southern Denmark, University of Southern Denmark, Hospital of Southern Jutland.
Institutional review board statement: The study was approved by the ethics committee of the region of southern Denmark (approval No: S20120176). Further, the study is included in the regional application to The Data Protection Agency (Institutional Southern Region of Denmark J.nr. 2008-58-0035). To ensure confidentiality direct paired comparisons between twin pairs are not shown.
Informed consent statement: Verbal as well as written informed consent was obtained from participants. This included consent to contact co-twins of the index twins, even if that included informing the co-twin of the diagnosis of the index twin.
Conflict-of-interest statement: Vibeke Andersen is an adviser for MSD/Merck, Jansen, and member of advisory board for MSD/Merck; Tine Jess has received funding for travel and speakers fee from AbbVie; Frederik Trier Moller, Lina Knudsen, Marcus Harbord, Jack Satsangi, Hannah Gordon, Lene Christiansen, Kaare Christensen: no conflicts of interest.
Data sharing statement: Technical appendix, code is available from the corresponding author at (frtm@ssi.dk). Additional data are available on request but may require further IRB approval/ approvals from the data protection agency, to be shared outside the research group.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Frederik Trier Moller, MD, PhD, Division of Epidemiology and Disease Surveillance Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark. frtm@ssi.dk
Telephone: +45-32-688696 Fax: +45-32-683874
Received: February 9, 2016
Peer-review started: February 10, 2016
First decision: March 7, 2016
Revised: March 21, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 7, 2016
Processing time: 110 Days and 21.8 Hours
Abstract

AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.

METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.

RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.

CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.

Keywords: Digestive system diseases; Inflammatory bowel diseases; Crohn’s disease; Ulcerative colitis; Epidemiologic studies; Twins; Biobank

Core tip: Using co-twin study designs to segregate genetic and environmental factors in inflammatory bowel diseases (IBD) holds promise for future discovery, considering subclinical disease in the co-twins. However, as MZ IBD discordant twins are rarely seen this often-mean insufficient power for planned analyses. Hence, collaboration between IBD twin resources is crucial.