Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

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Abstract
John Rioux and colleagues report results of a large genome-wide association meta-analysis and follow-up study of ulcerative colitis. They identify 29 new risk loci for this inflammatory disease and show that many risk loci are shared between ulcerative colitis and Crohn's disease. Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10−8), increasing the number of ulcerative colitis–associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.