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

Zhan Su, Laura J. Gay, Amy Strange, Claire Palles, Gavin Band, David C. Whiteman, Francesco Lescai, Cordelia Langford, Manoj Nanji, Sarah Edkins, Anouk van der Winkel, David Levine, Peter Sasieni, Celine Bellenguez, Kimberley Howarth, Colin Freeman, Nigel Trudgill, Art T. Tucker, Matti Pirinen, Maikel P. PeppelenboschLuc J. W. van der Laan, Ernst J. Kuipers, Joost P. H. Drenth, Wilbert H. Peters, John V. Reynolds, Dermot P. Kelleher, Ross McManus, Heike Grabsch, Hans Prenen, Raf Bisschops, Kausila Krishnadath, PD Siersema, Jantine W. P. M. van Baal, Mark Middleton, Russell Petty, Richard Gillies, Nicola Burch, Pradeep Bhandari, Stuart Paterson, Cathryn Edwards, Ian Penman, Kishor Vaidya, Yeng Ang, Iain Murray, Praful Patel, Weimin Ye, Paul Mullins, Anna H. Wu, Nigel C. Bird, Helen Dallal, ,

Research output: Contribution to journalArticleAcademicpeer-review

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 x 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 x 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.

Original languageEnglish
Pages (from-to)1131-+
Number of pages8
JournalNature Genetics
Volume44
Issue number10
DOIs
Publication statusPublished - Oct 2012

Keywords

  • GENOME-WIDE ASSOCIATION
  • GASTROESOPHAGEAL-REFLUX DISEASE
  • SUSCEPTIBILITY LOCI
  • RISK-FACTORS
  • ADENOCARCINOMA
  • CANCER
  • OBESITY
  • METAANALYSIS
  • POPULATION
  • METAPLASIA

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