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Meta-Analysis
. 2015 Sep;47(9):979-986.
doi: 10.1038/ng.3359. Epub 2015 Jul 20.

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

Collaborators, Affiliations
Free PMC article
Meta-Analysis

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

Jimmy Z Liu et al. Nat Genet. .
Free PMC article

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.

Conflict of interest statement

Competing financial interests

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Comparison of Crohn’s disease and ulcerative colitis risk variant odds ratios in Europeans and East Asians.
For each SNP, ORs (on the log-scale) were estimated within each population for Crohn’s disease (A) and ulcerative colitis (B). The colour of each point denotes the association P-value for that phenotype in East Asians. The red line denotes the best fitting least squares regression line, weighted by the inverse of the variance of the log ORs in East Asians. The significance and goodness of fit are shown in red.
Figure 2
Figure 2. Comparison of Variance explained per risk variant between East Asian and European Crohn’s Disease and ulcerative colitis.
Each box represents an independently associated SNP for Crohn’s disease (A) and ulcerative colitis (B). The size of each box is proportional to the amount of variance in disease liability explained by that variant. Only SNPs with an association P-value < 0.01 are included in the East Asian panel. The color of each box denotes whether any difference in variance explained is due to differences in allele frequencies (Fst > 0.1/monomorphic in East Asians), significant heterogeneity of odds ratios (P < 2.5×10−4) or both.

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