Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus

Su, Z., Gay, L. J., Strange, A., Palles, C., Band, G., Whiteman, D. C., Lescai, F., Langford, C., Nanji, M., Edkins, S., Van Der Winkel, A., Levine, D., Sasieni, P., Bellenguez, C., Howarth, K., Freeman, C., Trudgill, N., Tucker, A. T., Pirinen, M., Peppelenbosch, M. P., Van Der Laan, L. J. W., Kuipers, E. J., Drenth, J. P. H., Peters, W. H., Reynolds, J. V., Kelleher, D. P., McManus, R., Grabsch, H., Prenen, H., Bisschops, R., Krishnadath, K., Siersema, P. D., Van Baal, J. W. P. M., Middleton, M., Petty, R., Gillies, R., Burch, N., Bhandari, P., Paterson, S., Edwards, C., Penman, I., Vaidya, K., Ang, Y., Murray, I., Patel, P., Ye, W., Mullins, P., Wu, A. H., Bird, N. C., Dallal, H., Shaheen, N. J., Murray, L. J., Koss, K., Bernstein, L., Romero, Y., Hardie, L. J., Zhang, R., Winter, H., Corley, D. A., Panter, S., Risch, H. A., Reid, B. J., Sargeant, I., Gammon, M. D., Smart, H., Dhar, A., McMurtry, H., Ali, H., Liu, G., Casson, A. G., Chow, W. H., Rutter, M., Tawil, A., Morris, D., Nwokolo, C., Isaacs, P., Rodgers, C., Ragunath, K., MacDonald, C., Haigh, C., Monk, D., Davies, G., Wajed, S., Johnston, D., Gibbons, M., Cullen, S., Church, N., Langley, R., Griffin, M., Alderson, D., Deloukas, P., Hunt, S. E., Gray, E., Dronov, S., Potter, S. C., Tashakkori-Ghanbaria, A., Anderson, M., Brooks, C., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N., Trynka, G., Wijmenga, C., Cazier, J. B., Atherfold, P., Nicholson, A. M., Gellatly, N. L., Glancy, D., Cooper, S. C., Cunningham, D., Lind, T., Hapeshi, J., Ferry, D., Rathbone, B., Brown, J., Love, S., Attwood, S., MacGregor, S., Watson, P., Sanders, S., Ek, W., Harrison, R. F., Moayyedi, P., De Caestecker, J., Barr, H., Stupka, E., Vaughan, T. L., Peltonen, L., Spencer, C. C. A., Tomlinson, I., Donnelly, P., & Jankowski, J. A. Z. (2012) Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus. Nature Genetics, 44(10), pp. 1131-1136.

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Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.

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ID Code: 89327
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :50 Export Date: 21 September 2015 CODEN: NGENE Correspondence Address: Jankowski, J.A.Z.; Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, United Kingdom; email:
Keywords: allele, article, Barrett esophagus, chromosome 6p, controlled study, female, FOXF1 gene, gene, gene locus, genetic association, genetic predisposition, genetic risk, genetic susceptibility, genetic variability, genotype, human, major clinical study, major histocompatibility complex, male, obesity, organogenesis, priority journal, single nucleotide polymorphism, Adult, Aged, Case-Control Studies, Chromosomes, Human, Pair 16, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Middle Aged, Models, Genetic, Polymorphism, Single Nucleotide
DOI: 10.1038/ng.2408
ISSN: 10614036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Nature America Inc.
Deposited On: 20 Oct 2015 23:55
Last Modified: 24 Feb 2016 04:02

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