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Genome-wide association identifies multiple ulcerative colitis susceptibility loci.

Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
TitleGenome-wide association identifies multiple ulcerative colitis susceptibility loci.
Publication TypeJournal Article
Year of Publication2010
AuthorsMcGovern, DPB, Gardet, A, Törkvist, L, Goyette, P, Essers, J, Taylor, KD, Neale, BM, Ong, RTH, Lagacé, C, Li, C, Green, T, Stevens, CR, Beauchamp, C, Fleshner, PR, Carlson, M, D'Amato, M, Halfvarson, J, Hibberd, ML, Lördal, M, Padyukov, L, Andriulli, A, Colombo, E, Latiano, A, Palmieri, O, Bernard, E-J, Deslandres, C, Hommes, DW, de Jong, DJ, Stokkers, PC, Weersma, RK, Sharma, Y, Silverberg, MS, Cho, JH, Wu, J, Roeder, K, Brant, SR, L Schumm, P, Duerr, RH, Dubinsky, MC, Glazer, NL, Haritunians, T, Ippoliti, A, Melmed, GY, Siscovick, DS, Vasiliauskas, EA, Targan, SR, Annese, V, Wijmenga, C, Pettersson, S, Rotter, JI, Xavier, RJ, Daly, MJ, Rioux, JD, Seielstad, M
Corporate/Institutional AuthorsNIDDK IBD Genetics Consortium,
JournalNat Genet
Volume42
Issue4
Pagination332-7
Date Published2010 Apr
ISSN1546-1718
KeywordsColitis, Ulcerative, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Membrane Proteins, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Receptors, IgG
Abstract<p>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.</p>
DOI10.1038/ng.549
Alternate JournalNat. Genet.
PubMed ID20228799
PubMed Central IDPMC3087600
Grant ListM01-RR00425 / RR / NCRR NIH HHS / United States
DK043351 / DK / NIDDK NIH HHS / United States
RC1 DK086502 / DK / NIDDK NIH HHS / United States
R01 DK064869-07 / DK / NIDDK NIH HHS / United States
M01 RR000425-31 / RR / NCRR NIH HHS / United States
P30 DK040561 / DK / NIDDK NIH HHS / United States
U01 DK062413-08 / DK / NIDDK NIH HHS / United States
R01 DK060049 / DK / NIDDK NIH HHS / United States
P01 AI065687-040001 / AI / NIAID NIH HHS / United States
DK062422 / DK / NIDDK NIH HHS / United States
U01 DK062413 / DK / NIDDK NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01 HL087652-03 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
P01 DK046763-089001 / DK / NIDDK NIH HHS / United States
R21 DK084554 / DK / NIDDK NIH HHS / United States
RC1 DK086502-01 / DK / NIDDK NIH HHS / United States
DK064869 / DK / NIDDK NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
DK062423 / DK / NIDDK NIH HHS / United States
U01 HL080295-01 / HL / NHLBI NIH HHS / United States
AI067152 / AI / NIAID NIH HHS / United States
P30 DK040561-15 / DK / NIDDK NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
U01 DK062432 / DK / NIDDK NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 DK064869 / DK / NIDDK NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
R03 DK076984-02 / DK / NIDDK NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01 DK062429 / DK / NIDDK NIH HHS / United States
P30 DK063491-039004 / DK / NIDDK NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
U01 DK062423-06 / DK / NIDDK NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
U01 DK062420-07 / DK / NIDDK NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
U01 DK062422 / DK / NIDDK NIH HHS / United States
AI065687 / AI / NIAID NIH HHS / United States
DK83756 / DK / NIDDK NIH HHS / United States
P30 DK043351-18 / DK / NIDDK NIH HHS / United States
U01 DK062422-01 / DK / NIDDK NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
U19 AI067152-030006 / AI / NIAID NIH HHS / United States
DK062431 / DK / NIDDK NIH HHS / United States
P01 AI065687 / AI / NIAID NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
DK062420 / DK / NIDDK NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 DK083756-01 / DK / NIDDK NIH HHS / United States
R03 DK076984 / DK / NIDDK NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
U01 DK062432-08 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
U01 DK062423 / DK / NIDDK NIH HHS / United States
DK062429 / DK / NIDDK NIH HHS / United States
P01 DK046763-170001 / DK / NIDDK NIH HHS / United States
P01-DK046763 / DK / NIDDK NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
DK086502 / DK / NIDDK NIH HHS / United States
P01 DK046763 / DK / NIDDK NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
U01 DK062429-09 / DK / NIDDK NIH HHS / United States
R01 DK083756 / DK / NIDDK NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
DK062432 / DK / NIDDK NIH HHS / United States
DK062413 / DK / NIDDK NIH HHS / United States
U01 DK062420 / DK / NIDDK NIH HHS / United States
U01 DK062431-06 / DK / NIDDK NIH HHS / United States
U01 DK062431 / DK / NIDDK NIH HHS / United States
DK084554 / DK / NIDDK NIH HHS / United States
U19 AI067152 / AI / NIAID NIH HHS / United States
R21 DK084554-02 / DK / NIDDK NIH HHS / United States
DK76984 / DK / NIDDK NIH HHS / United States

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