Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Barrett, J. C., Lee, J. C., Lees, C. W., Prescott, N. J., Anderson, C. A., Phillips, A. and Brown, M. A. (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nature Genetics, 41 12: 1330-U99. doi:10.1038/ng.483


Author Barrett, J. C.
Lee, J. C.
Lees, C. W.
Prescott, N. J.
Anderson, C. A.
Phillips, A.
Brown, M. A.
Title Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2009-12
Year available 2009
Sub-type Article (original research)
DOI 10.1038/ng.483
Volume 41
Issue 12
Start page 1330
End page U99
Total pages 7
Editor M. Axton
Place of publication New York, N.Y. U.S.A.
Publisher Nature Publishing Group
Collection year 2010
Language eng
Subject C1
920105 Digestive System Disorders
920102 Cancer and Related Disorders
970111 Expanding Knowledge in the Medical and Health Sciences
970106 Expanding Knowledge in the Biological Sciences
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
110307 Gastroenterology and Hepatology
Abstract 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 times 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 times 10-17), 16q22 (CDH1 and CDH3; P = 2.8 times 10-8) and 7q31 (LAMB1; P = 3.0 times 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.
Keyword Inflammatory-bowel-disease
Intestinal Epithelial-cells
Crohns-disease
E-cadherin
Colorectal-cancer
Sequence Variants
Nuclear factor-4
Risk Loci
Gene
Expression
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Sun, 13 Dec 2009, 00:02:45 EST