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

By Jimmy Zhenli Liu, S. van Sommeren, Hailiang Huang, S. Ng, R. Alberts, A. Takahashi, S. Ripke, James C. Lee, L. Jostins, T. Shah and 31 more. 2015

2,354 citations recorded by the source corpus.

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.

Subfields: Genetics, Rheumatology

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Citations in the corpus

Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism (2016, neutral): “Disease GWAS studies evaluated include ASD 54 , schizophrenia 55 , inflammatory bowel disease 56 , type 2 diabetes mellitus 57 and serum lipid levels 58 .”
Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells (2016, background): “We focused on seven autoimmune diseases (celiac disease [CEL] [Dubois et al., 2010], inflammatory bowel disease [IBD] [Liu et al., 2015], including Crohn’s disease [CD] and ulcerative colitis [UC], multiple sclerosis [MS] [Beecham et al., 2013], type 1 diabetes [T1D] [Onengut-Gumuscu et al., 2015],…”
Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease (2016, methodology): “Barrett†,1 [1]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK”
Integrative functional genomic analysis of human brain development and neuropsychiatric risks (2018, methodology): “Toward this end, we collected GWAS data concerning neuropsychiatric disorders or personality traits including schizophrenia (SCZ) from CLOZUK (37), Alzheimer’s disease (AD) from IGAP (38), Parkinson’s disease (PD) (39), autism spectrum disorder (ASD) (40), attention deficit hyperactivity disorder (A”
Cellular and inter-cellular rewiring of the human colon during ulcerative colitis (2019, background): “Known disease risk alleles highlight key pathways in the pathogenesis of IBD, including innate and adaptive immunity, gut barrier function, and pathogen sensing and response (Liu et al., 2015; Rivas et al., 2011).”