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. Peppelenbosch; 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; Alan 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; Matthew 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; Janusz A. Z. Jankowski; Wellcome Trust Case Control Consor

doi:10.1038/ng.2408

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

Journal article

Peer reviewed

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, …

Nature genetics, Vol.44(10), pp.1131-+

01/10/2012

DOI: https://doi.org/10.1038/ng.2408

PMCID: PMC3459818

PMID: 22961001

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

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Title: Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Creators - without role: Zhan Su - Wellcome Trust
Laura J. Gay - Queen Mary University of London
Amy Strange - Wellcome Trust
Claire Palles - Wellcome Trust
Gavin Band - Wellcome Trust
David C. Whiteman - College Station Medical Center
Francesco Lescai - UCL, Inst Canc, London, England
Cordelia Langford - Wellcome Sanger Institute
Manoj Nanji - Queen Mary University of London
Sarah Edkins - Wellcome Sanger Institute
Anouk van der Winkel - College Station Medical Center
David Levine - University of Washington
Peter Sasieni - Supreme Council Of Health
Celine Bellenguez - Wellcome Trust
Kimberley Howarth - Wellcome Trust
Colin Freeman - Wellcome Trust
Nigel Trudgill - Sandwell Gen Hosp, Dept Gastroenterol, Lyndon, England
Art T. Tucker - Queen Mary University of London
Matti Pirinen - Wellcome Trust
Maikel P. Peppelenbosch - College Station Medical Center
Luc J. W. van der Laan - College Station Medical Center
Ernst J. Kuipers - College Station Medical Center
Joost P. H. Drenth - Radboud University Nijmegen
Wilbert H. Peters - Radboud University Nijmegen
John V. Reynolds - College Station Medical Center
Dermot P. Kelleher - Trinity Coll Dublin, Dublin, Ireland
Ross McManus - Trinity Coll Dublin, Dublin, Ireland
Heike Grabsch - University of Leeds
Hans Prenen - Univ Hosp Gasthuisberg, Dept Digest Oncol, B-3000 Louvain, Belgium
Raf Bisschops - Univ Hosp Gasthuisberg, Dept Digest Oncol, B-3000 Louvain, Belgium
Kausila Krishnadath - University of Amsterdam
Peter D. Siersema - College Station Medical Center
Jantine W. P. M. van Baal - College Station Medical Center
Mark Middleton - University of Oxford
Russell Petty - University of Aberdeen
Richard Gillies - University of Oxford
Nicola Burch - Leicester Royal Infirm, Ctr Digest Dis, Leicester, Leics, England
Pradeep Bhandari - Queen Alexandra Hosp, Gastroenterol & Hepatol Serv, Portsmouth, Hants, England
Stuart Paterson - Forth Valley Royal Hosp, Dept Gastroenterol, Larbert, England
Cathryn Edwards - Torbay Hosp, Dept Gastroenterol, Torquay, England
Ian Penman - Western Gen Hosp, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Kishor Vaidya - Victoria Hosp, Gastrointestinal Unit, Kirkcaldy, England
Yeng Ang - Natl Hlth Serv NHS Trust, Dept Gastroenterol, Royal Albert Edward Infirm, Wigan, England
Iain Murray - Royal Cornwall Hosp, Dept Gastroenterol, Truro, England
Praful Patel - Southampton Univ Hosp, NHS Trust, Dept Gastroenterol, Southampton, Hants, England
Weimin Ye - Karolinska Institutet
Paul Mullins - NHS Trust Royal Blackburn Hosp, E Lancashire Hosp, Dept Gastroenterol, Blackburn, Lancs, England
Anna H. Wu - College Station Medical Center
Nigel C. Bird - University of Sheffield
Helen Dallal - S Tees NHS Fdn Trust, Middlesbrough, Cleveland, England
Nicholas J. Shaheen - Supreme Council Of Health
Liam J. Murray - Queens University
Konrad Koss - Macclesfield Gen Hosp, Dept Gastroenterol, Macclesfield, Cheshire, England
Leslie Bernstein - Beckman Research Institute
Yvonne Romero - Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
Laura J. Hardie - University of Leeds
Rui Zhang - University of Washington
Helen Winter - Great Western Hosp, Dept Oncol, Swindon, Wilts, England
Douglas A. Corley - Kaiser Permanente
Simon Panter - S Tyneside Dist Hosp, Dept Gastroenterol, S Shields, England
Harvey A. Risch - Yale University
Brian J. Reid - Hutchinson
Ian Sargeant - Lister Hosp, Gastroenterol & Hepatol Serv, London, England
Marilie D. Gammon - Supreme Council Of Health
Howard Smart - Royal Liverpool Univ Hosp, Dept Gastroenterol, Liverpool, Merseyside, England
Anjan Dhar - Cty Durham & Darlington NHS Fdn Trust, Darlington, Durham, England
Hugh McMurtry - Lancashire Teaching Hosp NHS Fdn Trust, Chorley, England
Haythem Ali - Maidstone Hlth Author, Dept Surg, Maidstone, Kent, England
Geoffrey Liu - University of Toronto
Alan G. Casson - University of Saskatchewan
Wong-Ho Chow - NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Matt Rutter - Univ Hosp N Tees, Dept Gastroenterol, Stockton On Tees, England
Ashref Tawil - N Devon Dist Hosp, Gastroenterol & Hepatol Serv, Barnstaple, England
Danielle Morris - E&N Herts NHS Trust, Queen Elizabeth Hosp, Dept Gastroenterol, Welwyn Garden City, Herts, England
Chuka Nwokolo - Coventry
Peter Isaacs - Blackpool Victoria Hosp, Gastroenterol & Hepatol Serv, Blackpool, England
Colin Rodgers - Antrim & Whiteabbey United Hosp, Dept Gastroenterol, Whiteabbey, Antrim, North Ireland
Krish Ragunath - College Station Medical Center
Chris MacDonald - Cumberland Infirm, Gastroenterol Clin, Carlisle, England
Chris Haigh - Wansbeck Gen Hosp, Dept Gastroenterol, Ashington, England
David Monk - Countess Chester Hosp, Dept Gen Surg, Chester, Cheshire, England
Gareth Davies - Harrogate Dist Hosp, Gastroenterol & Hepatol Serv, Harrogate, England
Saj Wajed - Phillips Exeter Academy
David Johnston - Ninewells Hosp, Dept Gastroenterol, Dundee DD1 9SY, Scotland
Michael Gibbons - Craigavon Area Hosp, Dept Gastroenterol, Craigavon, England
Sue Cullen - Wycombe Hosp, Dept Gastroenterol, High Wycombe, Bucks, England
Nicholas Church - Royal Edinburgh Infirm, Ctr Liver & Digest Dis, Edinburgh, Midlothian, Scotland
Ruth Langley - Massachusetts Rehabilitation Commission
Michael Griffin - Royal Victoria Infirm, No Osophago Gastirc Unit, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
Derek Alderson - University of Birmingham
Panos Deloukas - Wellcome Sanger Institute
Sarah E. Hunt - Wellcome Sanger Institute
Emma Gray - Wellcome Sanger Institute
Serge Dronov - Wellcome Sanger Institute
Simon C. Potter - Wellcome Sanger Institute
Avazeh Tashakkori-Ghanbaria - Wellcome Sanger Institute
Mark Anderson - City Hosp Birmingham, Gastrointestinal Unit, Birmingham, W Midlands, England
Claire Brooks - University of Oxford
Jenefer M. Blackwell - University of Western Australia
Elvira Bramon - Kings Coll London, Dept Psychoisis Studies, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth,Inst Psychiat, London WC2R 2LS, England
Matthew A. Brown - University of Queensland
Juan P. Casas - UCL, Dept Epidemiol & Publ Hlth, London, England
Aiden Corvin - College Station Medical Center
Audrey Duncanson - Wellcome Trust
Hugh S. Markus - University of London
Christopher G. Mathew - College Station Medical Center
Colin N. A. Palmer - University of Dundee
Robert Plomin - Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England
Anna Rautanen - Wellcome Trust
Stephen J. Sawcer - University of Cambridge
Richard C. Trembath - College Station Medical Center
Ananth C. Viswanathan - Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England
Nicholas Wood - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Gosia Trynka - College Station Medical Center
Cisca Wijmenga - College Station Medical Center
Jean-Baptiste Cazier - Wellcome Trust
Paul Atherfold - UCB Pharma, Slough, Berks, England
Anna M. Nicholson - Queen Mary University of London
Nichola L. Gellatly - Queen Mary University of London
Deborah Glancy - Leicester Royal Infirm, Ctr Digest Dis, Leicester, Leics, England
Sheldon C. Cooper - Sandwell Gen Hosp, Dept Gastroenterol, Lyndon, England
David Cunningham - Royal Marsden Hosp, Gastrointestinal Unit, London SW3 6JJ, England
Tore Lind - AstraZeneca, Res & Dev, Lund, Sweden
Julie Hapeshi - Gloucestershire Royal Hosp, Gloucestershire Res & Dev Support Unit, Gloucester GL1 3NN, England
David Ferry - Royal Wolverhampton Hosp NHS Trust, New Cross Hosp, Dept Oncol, Wolverhampton, W Midlands, England
Barrie Rathbone - Leicester Royal Infirm, Ctr Digest Dis, Leicester, Leics, England
Julia Brown - College Station Medical Center
Sharon Love - College Station Medical Center
Stephen Attwood
Stuart MacGregor - College Station Medical Center
Peter Watson
Scott Sanders - Warwick Hosp, Dept Cellular Pathol, Warwick, England
Weronica Ek - College Station Medical Center
Rebecca F. Harrison - Leicester Royal Infirm, Dept Pathol, Leicester LE2 7LX, Leics, England
Paul Moayyedi - McMaster University
John de Caestecker - Leicester Gen Hosp, Dept Gastroenterol, Leicester LE5 4PW, Leics, England
Hugh Barr - Gloucestershire Royal Hosp, Dept Upper Gastrointestinal Surg, Gloucester GL1 3NN, England
Elia Stupka - Queen Mary University of London
Thomas L. Vaughan - Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA
Leena Peltonen
Chris C. A. Spencer - Wellcome Trust
Ian Tomlinson - Wellcome Trust
Peter Donnelly - Wellcome Trust
Janusz A. Z. Jankowski - Queen Mary University of London
Wellcome Trust Case Control Consor
Publication Details: Nature genetics, Vol.44(10), pp.1131-+
Publisher: Springer Nature
Number of pages: 8
Grant note: C548/A4584; D9612L00090 / Cancer Research UK (AspECT) University Hospitals of Leicester R and D grant UK National Blood Service controls C548/A9085 / Histological AssessmeNt Determining EpitheliaL Response (HANDEL) 085475/B/08/Z; 085475/Z/08/Z / WTCCC2 project AstraZeneca UK educational grant; AstraZeneca Wolfson-Royal Society Merit Award; Royal Society PDA/02/06/016; NF-SI-0611-10065; 05/12/01; NF-SI-0507-10379 / National Institute for Health Research; National Institute for Health Research (NIHR) R01CA13672501 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA G0000934 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) C548/A5675 / Esophageal Adenocarcinoma GenE Consortia incorporating the ChOPIN project HDRMJQ0 / AspECT Australian Research Council Australian National Health & Medical Research Council (NHMRC) Career Development Award; National Health and Medical Research Council (NHMRC) of Australia 09/IN.1/B2640 / Science Foundation Ireland 072894/Z/03/Z; 090532/Z/09/Z; 075491/Z/04/B; 068545/Z/02 / Wellcome Trust CZB/4/747; ETM/116 / Chief Scientist Office Health Research Board and the Wellcome Trust; Wellcome Trust MGAG1G7R / BOSS clinical trials project G0901310; G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 097364/Z/11/Z / Wellcome Trust Fellowship; Wellcome Trust G0901310; G0000934 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9921607208331
Academic Unit: King Abdulaziz University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article