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

Lookup NU author(s): Lynsey Cotterill, Dr John Mansfield

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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 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.

Publication metadata

Author(s): Barrett JC, Lee JC, Lees CW, Prescott NJ, Anderson CA, Phillips A, Wesley E, Parnell K, Zhang H, Drummond H, Nimmo ER, Massey D, Blaszczyk K, Elliott T, Cotterill L, Dallal H, Lobo AJ, Mowat C, Sanderson JD, Jewell DP, Newman WG, Edwards C, Ahmad T, Mansfield JC, Satsangi J, Parkes M, Mathew CG, Donnelly P, Peltonen L, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Craddock N, Deloukas P, Duncanson A, Jankowski J, Markus HS, McCarthy MI, Palmer CNA, Plomin R, Rautanen A, Sawcer SJ, Samani N, Trembath RC, Viswanathan AC, Wood N, Spencer CCA, Bellenguez C, Davison D, Freeman C, Strange A, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Perez ML, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P, Attwood AP, Stephens J, Sambrook J, Ouwehand WH, McArdle WL, Ring SM, Strachan DP, UK IBD Genetics Consortium, Wellcome Trust Case Control Consor, Management Comm, Data Anal Grp, DNA Genotyping Data QC Informatics, Publications Comm, UK Blood Serv Controls, 1958 Birth Cohort Controls

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2009

Volume: 41

Issue: 12

Pages: 1330-U99

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.483

DOI: 10.1038/ng.483

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