Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
PUBLISHED Ulcerative colitis (UC) is a common form of inflammatory bowel disease with a complex aetiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome- wide association scan for UC in 2361 cases and 5417 controls. Loci showing evidence of association at P < 1 ?...
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| Format: | Article in Journal/Newspaper |
| Language: | English |
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2009
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| Online Access: | http://hdl.handle.net/2262/66909 http://people.tcd.ie/acorvin |
| Summary: | PUBLISHED Ulcerative colitis (UC) is a common form of inflammatory bowel disease with a complex aetiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome- wide association scan for UC in 2361 cases and 5417 controls. Loci showing evidence of association at P < 1 ? 10 ?5 were followed up by genotyping in an independent set of 2321 cases and 4818 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 ? 10 ?17 ), 16q22 ( CDH1 and CDH3 P = 2.8 ? 10 ?8 ) and 7q31 ( LAMB1 3.0 ? 10 ?8 ). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, which is an established complication of longstanding UC. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of UC The principal funding for this study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project. We thank all subjects who contributed samples, and consultants and nursing staff across the UK who helped with recruitment of study subjects. We also thank Sami Bertrand, Jackie Bryant, Sarah L. Clark, Jen S. Conquer, Thomas Dibling, Stephen Gamble, Clifford Hind, Alicja Wilk, Claire R. Stribling, Sam Taylor, Julia C. Wyatt of the Wellcome Trust Sanger Institute's DNA Logistics and Genotyping Facility for technical assistance. Case collections were supported by the National Association for Colitis and Crohn's disease (NACC), the Wellcome Trust, the Medical Research Council UK, the Guy's and St Thomas' Charity, the Clinical Research Facility at the Peninsular College of Medicine and Dentistry, Exeter, the Torbay Hospital Medical Fund and the Evelyn Trust. We also acknowledge support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre awards to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London, the Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge School of Clinical Medicine and the Central Manchester Foundation Trust in partnership with the University of Manchester. We acknowledge use of the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02, and thank Professor Walter Bodmer and Dr Bruce Winney for use of the People of the British Isles DNA collection which was funded by the Wellcome Trust |
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