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

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

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Authors

  • 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. Peppelenbosch
  • And 124 others
  • Luc 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
  • Peter D. 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
  • Nicholas J. Shaheen
  • Liam J. Murray
  • Konrad Koss
  • Leslie Bernstein
  • Yvonne Romero
  • Laura J. Hardie
  • Rui Zhang
  • Helen Winter
  • Douglas .A. Corley
  • Simon Panter
  • Harvey A. Risch
  • Brian J. Reid
  • Ian Sargeant
  • Marilie D. Gammon
  • Howard Smart
  • Anjan Dhar
  • Hugh McMurtry
  • Haythem Ali
  • Geoffrey Liu
  • Allan G. Casson
  • Wong-Ho Chow
  • Matt Rutter
  • Ashref Tawil
  • Danielle Morris
  • Chuka Nwokolo
  • Peter Isaacs
  • Colin Rodgers
  • Krish Ragunath
  • Chris MacDonald
  • Chris Haigh
  • David Monk
  • Gareth Davies
  • Saj Wajed
  • David Johnston
  • Michael Gibbons
  • Sue Cullen
  • Nicholas Church
  • Ruth Langley
  • Michael Griffin
  • Derek Alderson
  • Panos Deloukas
  • Sarah E. Hunt
  • Emma Gray
  • Serge Dronov
  • Simon C. Potter
  • Avazeh Tashakkori-Ghanbaria
  • Mark Anderson
  • Claire Brooks
  • Jenefer M. Blackwell
  • Elvira Bramon
  • Mathew A. Brown
  • Juan P. Casas
  • Aiden Corvin
  • Audrey Duncanson
  • Hugh S. Markus
  • Christopher G. Mathew
  • Colin N.A. Palmer
  • Robert Plomin
  • Anna Rautanen
  • Stephen J. Sawcer
  • Richard C. Trembath
  • Ananth C. Viswanathan
  • Nicholas Wood
  • Gosia Trynka
  • Cisca Wijmenga
  • Jean-Baptiste Cazier
  • Paul Atherfold
  • Anna M. Nicholson
  • Nichola L. Gellatly
  • Deborah Glancy
  • Sheldon C. Cooper
  • David Cunningham
  • Tore Lind
  • Julie Hapeshi
  • David Ferry
  • Barrie Rathbone
  • Julia Brown
  • Sharon Love
  • Stephen Attwood
  • Stuart MacGregor
  • Peter Watson
  • Scott Sanders
  • Weronica Ek
  • Rebecca F. Harrison
  • Paul Moayyedi
  • John De Caestecker
  • Hugh Barr
  • Elia Stupka
  • Thomas L. Vaughan
  • Leena Peltonen
  • Chris C.A. Spencer
  • Ian Tomlinson
  • Peter Donnelly
  • Janus A.Z. Jankowski

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Info

Original languageEnglish
Pages1131-1136
Number of pages6
JournalNature Genetics
Journal publication date2012
Journal number10
Volume44
DOIs
StatePublished

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 ; 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 ; 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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