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


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, CN; Plomin, R; Rautanen, A; Sawcer, SJ; Samani, N; Trembath, RC; Viswanathan, AC; Wood, N; Spencer, CC; 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; (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nature genetics, 41 (12). pp. 1330-4. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.483

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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.

Item Type: Article
Keywords: Cadherins/*genetics, Case-Control Studies, Chromosomes, Human, Pair 20/*genetics, Colitis, Ulcerative/epidemiology/*genetics/pathology, *Genetic Predisposition to Disease, Genome-Wide Association Study, Hepatocyte Nuclear Factor 4/*genetics, Humans, Laminin/*genetics, Cadherins, genetics, Case-Control Studies, Chromosomes, Human, Pair 20, genetics, Colitis, Ulcerative, epidemiology, genetics, pathology, Genetic Predisposition to Disease, Genome-Wide Association Study, Hepatocyte Nuclear Factor 4, genetics, Humans, Laminin, genetics
Faculty and Department: Distance Learning
Academic Services & Administration > Distance Learning

Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 19915572
Web of Science ID: 272144900016
URI: http://researchonline.lshtm.ac.uk/id/eprint/4283

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