Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Liu, Jimmy Z; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Hee Cheon, Jae; Cho, Judy; Daryani, Naser E; Franke, Lude; Hawkey, Chris; Fuyuno, Yuta; Lewis, Nina; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Ho Kim, Won; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph J Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Multiple Sclerosis Genetics Consortium, International; IBD Genetics Consortium, International; Barrett, Jeffrey C; Franke, Andre; Alizadeh, Behrooz Z; Parkes, Miles; K, Thelma B; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

Abstract

Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 andATG16L1) or a combination of these factors (IL23R andIRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

• Journal Article Type: Article
• Acceptance Date: Jun 24, 2015
• Online Publication Date: Jul 20, 2015
• Publication Date: Sep 1, 2015
• Deposit Date: Nov 24, 2016
• Journal: Nature Genetics
• Print ISSN: 1061-4036
• Electronic ISSN: 1546-1718
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 47
• Issue: 9
• Pages: 979–986
• DOI: https://doi.org/10.1038/ng.3359
• Public URL: https://nottingham-repository.worktribe.com/output/1118227
• Publisher URL: https://www.nature.com/articles/ng.3359
• PMID: 00036039
• Additional Information: Liu, J., van Sommeren, S., Huang, H. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47, 979–986 (2015). https://doi.org/10.1038/ng.3359; ; Full list of authors is available from the publisher page for this article.