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

Barrett, Jeffrey C, Lee, James C, Lees, Charles W, Prescott, Natalie J, Anderson, Carl A, Phillips, Anne, Wesley, Emma, Parnell, Kirstie, Zhang, Hu, Drummond, Hazel, Nimmo, Elaine R, Massey, Dunecan, Blaszczyk, Kasia, Elliott, Timothy, Cotterill, Lynn, Dallal, Helen, Lobo, Alan J, Mowat, Craig, Sanderson, Jeremy D, Jewell, Derek P, Newman, William G, Edwards, Cathryn, Ahmad, Tariq, Mansfield, John C, Satsangi, Jack, Parkes, Miles, Mathew, Christopher G, Donnelly, Peter, Peltonen, Leena, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Craddock, Nicholas John, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, McCarthy, Mark I, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Samani, Nilesh, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Spencer, Chris C A, Barrett, Jeffrey C, Bellenguez, Céline, Davison, Daniel, Freeman, Colin, Strange, Amy, Donnelly, Peter, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Perez, Marc L, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Deloukas, Panos, Peltonen, Leena, Mathew, Christopher G, Blackwell, Jenefer M, Brown, Matthew A, Corvin, Aiden, McCarthy, Mark I, Spencer, Chris C A, Attwood, Antony P, Stephens, Jonathan, Sambrook, Jennifer, Ouwehand, Willem H, McArdle, Wendy L, Ring, Susan M and Strachan, David P 2009. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nature Genetics 41 (12) , pp. 1330-1334. 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 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 10-17), 16q22 (CDH1 and CDH3; P = 2.8 10-8) and 7q31 (LAMB1; P = 3.0 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
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine
Publisher: Nature Publishing Group
ISSN: 1061-4036
Last Modified: 04 Jun 2017 03:58
URI: http://orca-mwe.cf.ac.uk/id/eprint/29867

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