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

Jeffrey C Barrett, James C Lee, Charles W Lees, Natalie J Prescott, Carl A Anderson, Anne Phillips, Emma Wesley, Kirstie Parnell, Hu Zhang, Hazel Drummond, Elaine R Nimmo, Dunecan Massey, Kasia Blaszczyk, Timothy Elliott, Lynn Cotterill, Helen Dallal, Alan J Lobo, Craig Mowat, Jeremy D Sanderson, Derek P JewellWilliam G Newman, Cathryn Edwards, Tariq Ahmad, John C Mansfield, Jack Satsangi, Miles Parkes, Christopher G Mathew, Peter Donnelly, Leena Peltonen, Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Nicholas Craddock, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S Markus, Christopher G Mathew, Mark I McCarthy, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen J Sawcer, Nilesh Samani, Richard C Trembath, Anath C Viswanathan, Wendy L McArdle, Susan M Ring, UK IBD Genetics Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

365 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1330-4
Number of pages5
JournalNature Genetics
Volume41
Issue number12
DOIs
Publication statusPublished - 2009

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