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Genome-wide association identifies multiple ulcerative colitis susceptibility loci

Open access
The NIDDK IBD Genetics Consortium, McGovern, Dermot P B, Gardet, Agnès, Törkvist, Leif, Goyette, Philippe, Essers, Jonah, Taylor, Kent D, Neale, Benjamin M, Ong, Rick T H, Lagacé, Caroline, Li, Chun, Green, Todd, Stevens, Christine R, Beauchamp, Claudine, Fleshner, Phillip R, Carlson, Marie, D'Amato, Mauro, Halfvarson, Jonas, Hibberd, Martin L, Lördal, Mikael, Padyukov, Leonid, Andriulli, Angelo, Colombo, Elisabetta, Latiano, Anna, Palmieri, Orazio, Bernard, Edmond-Jean, Deslandres, Colette, Hommes, Daan W, de Jong, Dirk J, Stokkers, Pieter C, Weersma, Rinse K, Sharma, Yashoda, Silverberg, Mark S, Cho, Judy H, Wu, Jing, Roeder, Kathryn, Brant, Steven R, Schumm, L Phillip, Duerr, Richard H, Dubinsky, Marla C, Glazer, Nicole L, Haritunians, Talin, Ippoliti, Andy, Melmed, Gil Y, Siscovick, David S, Vasiliauskas, Eric A, Targan, Stephan R, Annese, Vito, Wijmenga, Cisca, Pettersson, Sven, Rotter, Jerome I, Xavier, Ramnik J, Daly, Mark J, Rioux, John D, Seielstad, Mark·2010·Nature Genetics

Abstract

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 × 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 × 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.

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Metadata

Authors
The NIDDK IBD Genetics Consortium, McGovern, D. P. B., Gardet, A., Törkvist, L., Goyette, P., Essers, J., Taylor, K. D., Neale, B. M., Ong, R. T. H., Lagacé, C., Li, C., Green, T., Stevens, C. R., Beauchamp, C., Fleshner, P. R., Carlson, M., D'Amato, M., Halfvarson, J., Hibberd, M. L., Lördal, M., Padyukov, L., Andriulli, A., Colombo, E., Latiano, A., Palmieri, O., Bernard, E.-J., Deslandres, C., Hommes, D. W., de Jong, D. J., Stokkers, P. C., Weersma, R. K., Sharma, Y., Silverberg, M. S., Cho, J. H., Wu, J., Roeder, K., Brant, S. R., Schumm, L. P., Duerr, R. H., Dubinsky, M. C., Glazer, N. L., Haritunians, T., Ippoliti, A., Melmed, G. Y., Siscovick, D. S., Vasiliauskas, E. A., Targan, S. R., Annese, V., Wijmenga, C., Pettersson, S., Rotter, J. I., Xavier, R. J., Daly, M. J., Rioux, J. D., & Seielstad, M.
Venue
Nature Genetics
Published
2010-03-14
Volume
42
Issue
4
Pages
332-337
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2109899118
Cited by
654
References
6
FWCI
39.23
Type
journal article
Language
en
Open access
green

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