Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region
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., Mowat, C., Sanderson, J. D., Jewell, D. P., Newman, W. G., Edwards, C., Ahmad, T., Mansfield, J. C., Satsangi, J., Parkes, M., Mathew, C. G., Donnelly, P., Peltonen, L., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Craddock, N., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H. S., McCarthy, M. I., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Samani, N., Trembath, R. C., Viswanathan, A. C., Wood, N., Spencer, C. C. A., Bellenguez, C., Davison, D., Freeman, C., Strange, A., Langford, C., Hunt, S. E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O. T., Liddle, J., Perez, M. L., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Spencer, C. C. A., Attwood, A. P., Stephens, J., Sambrook, J., Ouwehand, W. H., McArdle, W. L., Ring, S. M., & Strachan, D. 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.
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. © 2009 Nature America, Inc. All rights reserved.
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|Item Type:||Journal Article|
|Additional Information:||Cited By :219 Export Date: 21 September 2015 CODEN: NGENE Correspondence Address: Barrett, J. C.; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; email: email@example.com|
|Keywords:||hepatocyte nuclear factor 4alpha, uvomorulin, adult, article, CDH1 gene, chromosome 16q, chromosome 20q, colorectal cancer, controlled study, gene, gene locus, genetic association, genetic susceptibility, genome, genotype, hepatocyte nuclear factor 4alpha gene, human, intestine epithelium cell, major clinical study, priority journal, ulcerative colitis, Cadherins, Case-Control Studies, Chromosomes, Human, Pair 20, Colitis, Ulcerative, Genetic Predisposition to Disease, Genome-Wide Association Study, Hepatocyte Nuclear Factor 4, Humans, Laminin|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2009 Nature America Inc|
|Deposited On:||23 Oct 2015 00:01|
|Last Modified:||22 Aug 2016 23:08|
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