Genome-wide association identifies multiple ulcerative colitis susceptibility loci

• DOI: 10.1038/ng.549
• Publication Date: 2010-03-14T18:42:12Z
• Authors: Dermot P B McGovern; Agnès Gardet; Leif Törkvist; Philippe Goyette; Jonah Essers; Kent D Taylor; Benjamin M Neale; Rick T H Ong; Caroline Lagacé; Chun Li; Todd Green; Christine R Stevens; Claudine Beauchamp; Phillip R Fleshner; Marie Carlson; Mauro D'Amato; Jonas Halfvarson; Martin L Hibberd; Mikael Lördal; Leonid Padyukov; Angelo Andriulli; Elisabetta Colombo; Anna Latiano; Orazio Palmieri; Edmond-Jean Bernard; Colette Deslandres; Daan W Hommes; Dirk J de Jong; Pieter C Stokkers; Rinse K Weersma; Yashoda Sharma; Mark S Silverberg; Judy H Cho; Jing Wu; Kathryn Roeder; Steven R Brant; L Phillip Schumm; Richard H Duerr; Marla C Dubinsky; Nicole L Glazer; Talin Haritunians; Andy Ippoliti; Gil Y Melmed; David S Siscovick; Eric A Vasiliauskas; Stephan R Targan; Vito Annese; Cisca Wijmenga; Sven Pettersson; Jerome I Rotter; Ramnik J Xavier; Mark J Daly; John D Rioux; Mark Seielstad
• Keywords: RISK; 0301 basic medicine; Receptors, IgG; Membrane Proteins; IMMUNITY; Polymorphism, Single Nucleotide; CROHNS-DISEASE; 3. Good health; 03 medical and health sciences; IGMD 2: Molecular gastro-enterology and hepatology; RETICULUM STRESS-RESPONSE; Meta-Analysis as Topic; GENETIC-VARIANTS; Humans; Colitis, Ulcerative; Genetic Predisposition to Disease; CONTRIBUTE; POPULATION; INFLAMMATORY-BOWEL-DISEASE; Genome-Wide Association Study

Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.