Journal
NATURE GENETICS
Volume 42, Issue 4, Pages 332-U88Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.549
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Categories
Funding
- US National Center for Research Resources (NCRR) [M01-RR00425]
- US National Institutes of Health/NIDDK [P01-DK046763, DK83756, DK086502, DK043351, DK062431, DK062422, DK062420, DK062432, DK062423, DK062413, DK062429]
- Diabetes Endocrinology Research Center [DK063491]
- Cedars-Sinai Medical Center
- US National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652]
- US National Institute of Neurological Disorders and Stroke
- Crohn's and Colitis Foundation of America
- Bohmfalk Funds for Medical Research
- Burroughs Wellcome Medical Foundation
- US National Institute of Allergy and Infectious Diseases [AI065687, AI067152]
- US National Institute of Diabetes and Digestive and Kidney Diseases [DK064869]
- Swedish Society of Medicine
- Bengt Ihre Foundation
- Karolinska Institutet
- Swedish National Program for IBD Genetics
- Swedish Organization for IBD
- Swedish Medical Research Council
- Soderbergh Foundation
- Swedish Cancer Foundation
- [DK76984]
- [DK084554]
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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(1), 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.
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