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

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.