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

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

Research output: Contribution to journalArticleResearchpeer-review

1547 Citations (Scopus)


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 and ATG16L1) or a combination of these factors (IL23R and IRGM). 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.

Original languageEnglish
Pages (from-to)979-986
Number of pages8
JournalNature Genetics
Issue number9
Publication statusPublished - Sept 2015
Externally publishedYes

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