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

UK IBD Genetics Consortium, Wellcome Trust Case Control Consortium 2, 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 MowatJeremy D. Sanderson, Derek P. Jewell, William 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, Mark I. McCarthy, Colin N. A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Nilesh Samani, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Chris C. A. Spencer, Celine Bellenguez, Wellcome Trust Case Control Consortium 2

    Research output: Contribution to journalArticle

    347 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-U99
    Number of pages7
    JournalNature Genetics
    Volume41
    Issue number12
    DOIs
    Publication statusPublished - Dec 2009

    Keywords

    • INFLAMMATORY-BOWEL-DISEASE
    • INTESTINAL EPITHELIAL-CELLS
    • CROHNS-DISEASE
    • E-CADHERIN
    • COLORECTAL-CANCER
    • SEQUENCE VARIANTS
    • NUCLEAR FACTOR-4
    • RISK LOCI
    • GENE
    • EXPRESSION

    Cite this

    UK IBD Genetics Consortium, Wellcome Trust Case Control Consortium 2, Barrett, J. C., Lee, J. C., Lees, C. W., Prescott, N. J., Anderson, C. A., Phillips, A., Wesley, E., Parnell, K., Zhang, H., Drummond, H., Nimmo, E. R., Massey, D., Blaszczyk, K., Elliott, T., Cotterill, L., Dallal, H., Lobo, A. J., ... Wellcome Trust Case Control Consortium 2 (2009). Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nature Genetics, 41(12), 1330-U99. https://doi.org/10.1038/ng.483