1. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
- Author
-
Nicholas W. Wood, Chris C. A. Spencer, Konrad Koss, Heike I. Grabsch, Ananth C. Viswanathan, Simon C. Potter, Thomas L. Vaughan, Brian J. Reid, Céline Bellenguez, Kimberley Howarth, Claire Brooks, Michael Gibbons, Geoffrey Liu, David Ferry, Ian Tomlinson, Chuka U. Nwokolo, John de Caestecker, Barrie Rathbone, Francesco Lescai, Anna Rautanen, Weimin Ye, Nicholas I. Church, Nigel C. Bird, Laura J. Hardie, Peter H. Watson, Ross McManus, Peter Donnelly, David Cunningham, Peter Sasieni, Aiden Corvin, Cisca Wijmenga, Sarah Edkins, Amy Strange, Sheldon C. Cooper, Audrey Duncanson, Harvey A. Risch, Ian Sargeant, Christopher Macdonald, Pradeep Bhandari, Sarah E. Hunt, Matthew D. Rutter, John V. Reynolds, Nigel Trudgill, Rebecca Harrison, Anna H. Wu, Scott Sanders, Christopher G. Mathew, Mark S. Anderson, Raf Bisschops, Cathryn Edwards, Avazeh Tashakkori-Ghanbaria, Praful Patel, Wong Ho Chow, Anouk Van Der Winkel, Panos Deloukas, Kishor Vaidya, Manoj Nanji, Nichola L. Gellatly, Leena Peltonen, Iain A. Murray, Matthew A. Brown, Deborah Glancy, Marilie D. Gammon, Robert Plomin, Julie Hapeshi, Elia Stupka, Janusz Jankowski, Liam J. Murray, Alan G. Casson, Hugh McMurtry, Haythem Ali, Douglas A. Corley, Kausila Krishnadath, Hugh Barr, David Johnston, Derek Alderson, Ruth E Langley, Elvira Bramon, Saj Wajed, Sharon Love, Peter D. Siersema, Ernst J. Kuipers, Simon Panter, Mark R. Middleton, Ian D. Penman, Peter Isaacs, Krish Ragunath, David K. Levine, Paul Atherfold, Maikel P. Peppelenbosch, Joost P.H. Drenth, Claire Palles, Art Tucker, Stephen Attwood, Cordelia Langford, Rui Zhang, Matti Pirinen, Colin Freeman, Stephen Sawcer, Stuart MacGregor, Hugh S. Markus, S Paterson, Anna M. Nicholson, M Griffin, Nicola Burch, Colin Rodgers, Helen Winter, Anjan Dhar, Zhan Su, Emma Gray, Jantine W. P. M. van Baal, Richard C. Trembath, David Monk, Paul Mullins, Danielle Morris, Ashref Tawil, Serge Dronov, Hans Prenen, Yeng Ang, Dermot Kelleher, Gavin Band, Leslie Bernstein, Weronica E. Ek, H Smart, Luc J. W. van der Laan, Colin N. A. Palmer, Jenefer M. Blackwell, Wilbert H.M. Peters, David C. Whiteman, Tore Lind, Gosia Trynka, Helen Dallal, Paul Moayyedi, Russell D. Petty, Richard S. Gillies, Nicholas J. Shaheen, Chris Haigh, Sue Cullen, Gareth E. Davies, Julia Brown, Jean-Baptiste Cazier, Juan P. Casas, Yvonne Romero, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Gastroenterology & Hepatology, and Surgery
- Subjects
Male ,Linkage disequilibrium ,Genome-wide association study ,GASTROESOPHAGEAL-REFLUX DISEASE ,Barrett’s Esophagus ,Gastroenterology ,Linkage Disequilibrium ,Major Histocompatibility Complex ,0302 clinical medicine ,Gene Frequency ,Metaplasia ,Molecular gastro-enterology and hepatology Membrane transport and intracellular motility [IGMD 2] ,POPULATION ,Gastro-esophageal reflux disease (GERD) ,Genetics ,education.field_of_study ,Single nucleotide polymorphisms (SNPs) ,Middle Aged ,CANCER ,3. Good health ,Esophageal adenocarcinoma (EAC) ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,OBESITY ,Adenocarcinoma ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Molecular gastro-enterology and hepatology Translational research [IGMD 2] ,Adult ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,Population ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Article ,Genome-wide association (GWA) study ,Barrett Esophagus ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Esophagus ,GENOME-WIDE ASSOCIATION ,education ,METAANALYSIS ,Aged ,Models, Genetic ,ADENOCARCINOMA ,medicine.disease ,digestive system diseases ,Genetic Loci ,Case-Control Studies ,Barrett's esophagus ,RISK-FACTORS ,METAPLASIA ,Human medicine ,Chromosomes, Human, Pair 16 ,Genome-Wide Association Study - Abstract
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.
- Published
- 2012
- Full Text
- View/download PDF