Association Analyses Identify 38 Susceptibility Loci for Inflammatory Bowel Disease and Highlight Shared Genetic Risk Across Populations

Overview

Journal Nat Genet

Specialty Genetics

Date 2015 Jul 21

PMID 26192919

Citations 1272

Authors

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 Dayani

Lude Franke

Yuta Fuyuno

Ailsa Hart

Ramesh C Juyal

Garima Juyal

Won Ho Kim

Andrew P Morris

Hossein Poustchi

William G Newman

Vandana Midha

Timothy R Orchard

Homayon Vahedi

Ajit Sood

Joseph Y Sung

Reza Malekzadeh

Harm-Jan Westra

Keiko Yamazaki

Suk-Kyun Yang

Jeffrey C Barrett

Behrooz Z Alizadeh

Miles Parkes

Thelma Bk

Mark J Daly

Michiaki Kubo

Carl A Anderson

Rinse K Weersma

Affiliations

Soon will be listed here.

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 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.

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