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


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.

SUBMITTER: UK IBD Genetics Consortium 

PROVIDER: S-EPMC2812019 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

Barrett Jeffrey C JC   Lee James C JC   Lees Charles W CW   Prescott Natalie J NJ   Anderson Carl A CA   Phillips Anne A   Wesley Emma E   Parnell Kirstie K   Zhang Hu H   Drummond Hazel H   Nimmo Elaine R ER   Massey Dunecan D   Blaszczyk Kasia K   Elliott Timothy T   Cotterill Lynn L   Dallal Helen H   Lobo Alan J AJ   Mowat Craig C   Sanderson Jeremy D JD   Jewell Derek P DP   Newman William G WG   Edwards Cathryn C   Ahmad Tariq T   Mansfield John C JC   Satsangi Jack J   Parkes Miles M   Mathew Christopher G CG   Donnelly Peter P   Peltonen Leena L   Blackwell Jenefer M JM   Bramon Elvira E   Brown Matthew A MA   Casas Juan P JP   Corvin Aiden A   Craddock Nicholas N   Deloukas Panos P   Duncanson Audrey A   Jankowski Janusz J   Markus Hugh S HS   Mathew Christopher G CG   McCarthy Mark I MI   Palmer Colin N A CN   Plomin Robert R   Rautanen Anna A   Sawcer Stephen J SJ   Samani Nilesh N   Trembath Richard C RC   Viswanathan Anath C AC   Wood Nicholas N   Spencer Chris C A CC   Barrett Jeffrey C JC   Bellenguez Céline C   Davison Daniel D   Freeman Colin C   Strange Amy A   Donnelly Peter P   Langford Cordelia C   Hunt Sarah E SE   Edkins Sarah S   Gwilliam Rhian R   Blackburn Hannah H   Bumpstead Suzannah J SJ   Dronov Serge S   Gillman Matthew M   Gray Emma E   Hammond Naomi N   Jayakumar Alagurevathi A   McCann Owen T OT   Liddle Jennifer J   Perez Marc L ML   Potter Simon C SC   Ravindrarajah Radhi R   Ricketts Michelle M   Waller Matthew M   Weston Paul P   Widaa Sara S   Whittaker Pamela P   Deloukas Panos P   Peltonen Leena L   Mathew Christopher G CG   Blackwell Jenefer M JM   Brown Matthew A MA   Corvin Aiden A   McCarthy Mark I MI   Spencer Chris C A CC   Attwood Antony P AP   Stephens Jonathan J   Sambrook Jennifer J   Ouwehand Willem H WH   McArdle Wendy L WL   Ring Susan M SM   Strachan David P DP  

Nature genetics 20091115 12


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 bio  ...[more]

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