Journal
NATURE GENETICS
Volume 41, Issue 12, Pages 1330-U99Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.483
Keywords
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Categories
Funding
- Wellcome Trust [083948/Z/07/Z, 068545/Z/02]
- National Association for Colitis and Crohn's Disease (NACC)
- Medical Research Council UK
- Guy's and St. Thomas' Charity
- Clinical Research Facility at the Peninsular College of Medicine and Dentistry, Exeter
- Torbay Hospital Medical Fund
- Evelyn Trust
- Wolfson-Royal Society Merit Award
- UK Medical Research Council [G0601387]
- Special Trustees of Moorfields National Health Service (NHS) Foundation Trust
- Department of Health via the National Institute for Health Research (NIHR)
- Cambridge University Hospitals NHS Foundation
- Central Manchester NHS Foundation Trust in partnership with the University of Manchester
- Moorfields Eye Hospital in partnership with University College London Institute of Ophthalmology
- Medical Research Council [G0000934]
- Chief Scientist Office [CZB/4/540] Funding Source: researchfish
- Medical Research Council [G9817803B, G0800509, G0600329, G0800675, G19/2, G0000934, G0800383, G0800759, G0601387, MC_qA137934] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10379, PDA/02/06/016] Funding Source: researchfish
- MRC [MC_qA137934, G0800675, G0601387, G0800759, G0800509, G0800383, G19/2, G0000934, G0600329] Funding Source: UKRI
- Wellcome Trust [083948/Z/07/Z] Funding Source: Wellcome Trust
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Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P < 1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.
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