TY - JOUR T1 - Genome-wide association identifies multiple ulcerative colitis susceptibility loci. JF - Nat Genet Y1 - 2010 A1 - McGovern, Dermot P B A1 - Gardet, Agnès A1 - Törkvist, Leif A1 - Goyette, Philippe A1 - Essers, Jonah A1 - Taylor, Kent D A1 - Neale, Benjamin M A1 - Ong, Rick T H A1 - Lagacé, Caroline A1 - Li, Chun A1 - Green, Todd A1 - Stevens, Christine R A1 - Beauchamp, Claudine A1 - Fleshner, Phillip R A1 - Carlson, Marie A1 - D'Amato, Mauro A1 - Halfvarson, Jonas A1 - Hibberd, Martin L A1 - Lördal, Mikael A1 - Padyukov, Leonid A1 - Andriulli, Angelo A1 - Colombo, Elisabetta A1 - Latiano, Anna A1 - Palmieri, Orazio A1 - Bernard, Edmond-Jean A1 - Deslandres, Colette A1 - Hommes, Daan W A1 - de Jong, Dirk J A1 - Stokkers, Pieter C A1 - Weersma, Rinse K A1 - Sharma, Yashoda A1 - Silverberg, Mark S A1 - Cho, Judy H A1 - Wu, Jing A1 - Roeder, Kathryn A1 - Brant, Steven R A1 - Schumm, L Phillip A1 - Duerr, Richard H A1 - Dubinsky, Marla C A1 - Glazer, Nicole L A1 - Haritunians, Talin A1 - Ippoliti, Andy A1 - Melmed, Gil Y A1 - Siscovick, David S A1 - Vasiliauskas, Eric A A1 - Targan, Stephan R A1 - Annese, Vito A1 - Wijmenga, Cisca A1 - Pettersson, Sven A1 - Rotter, Jerome I A1 - Xavier, Ramnik J A1 - Daly, Mark J A1 - Rioux, John D A1 - Seielstad, Mark KW - Colitis, Ulcerative KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Humans KW - Membrane Proteins KW - Meta-Analysis as Topic KW - Polymorphism, Single Nucleotide KW - Receptors, IgG AB -

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.

VL - 42 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20228799?dopt=Abstract ER -