Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Jeffrey C. Barrett; James C. Lee; Charles W. Lees; Natalie J. Prescott; Carl A. Anderson; Anne Phillips; Emma Wesley; Kirstie Parnell; Hu Zhang; Hazel Drummond; Elaine R. Nimmo; Dunecan Massey; Kasia Blaszczyk; Timothy Elliott; Lynn Cotterill; Helen Dallal; Alan J. Lobo; Craig Mowat; Jeremy D. Sanderson; Derek P. Jewell; William G. Newman; Cathryn Edwards; Tariq Ahmad; John C. Mansfield; Jack Satsangi; Miles Parkes; Christopher G. Mathew; Peter Donnelly; Leena Peltonen; Jenefer M. Blackwell; Elvira Bramon; Matthew A. Brown; Juan P. Casas; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Audrey Duncanson; Janusz Jankowski; Hugh S. Markus; Mark I. McCarthy; Colin N. A. Palmer; Robert Plomin; Anna Rautanen; Stephen J. Sawcer; Nilesh Samani; Richard C. Trembath; Ananth C. Viswanathan; Nicholas Wood; Chris C. A. Spencer; Celine Bellenguez; Daniel Davison; Colin Freeman; Amy Strange; Cordelia Langford; Sarah E. Hunt; Sarah Edkins; Rhian Gwilliam; Hannah Blackburn; Suzannah J. Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T. McCann; Jennifer Liddle; Marc L. Perez; Simon C. Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Antony P. Attwood; Jonathan Stephens; Jennifer Sambrook; Willem H. Ouwehand; Wendy L. McArdle; Susan M. Ring; David P. Strachan; 1958 Birth Cohort Controls

doi:10.1038/ng.483

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Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Journal article

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Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Jeffrey C. Barrett, James C. Lee, Charles W. Lees, Natalie J. Prescott, Carl A. Anderson, Anne Phillips, Emma Wesley, Kirstie Parnell, Hu Zhang, Hazel Drummond, …

Nature genetics, Vol.41(12), pp.1330-U99

01/12/2009

DOI: https://doi.org/10.1038/ng.483

PMCID: PMC2812019

PMID: 19915572

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P < 1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.

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Title: Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region
Creators - without role: Jeffrey C. Barrett - Wellcome Sanger Institute
James C. Lee - Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge, England
Charles W. Lees - University of Edinburgh
Natalie J. Prescott - Supreme Council Of Health
Carl A. Anderson - Wellcome Sanger Institute
Anne Phillips - University of Edinburgh
Emma Wesley - Phillips Exeter Academy
Kirstie Parnell - Phillips Exeter Academy
Hu Zhang - Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge, England
Hazel Drummond - University of Edinburgh
Elaine R. Nimmo - University of Edinburgh
Dunecan Massey - Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge, England
Kasia Blaszczyk - Supreme Council Of Health
Timothy Elliott - St Thomas Hosp, Dept Gastroenterol, Guys & St Thomas NHS Fdn Trust, London, England
Lynn Cotterill - University of Manchester
Helen Dallal - James Cook University
Alan J. Lobo - University of Sheffield
Craig Mowat
Jeremy D. Sanderson - St Thomas Hosp, Dept Gastroenterol, Guys & St Thomas NHS Fdn Trust, London, England
Derek P. Jewell - Radcliffe Infirm, Gastroenterol Unit, Gibson Labs, Oxford OX2 6HE, England
William G. Newman - Cent Manchester NHS Fdn Trust, NIHR Biomed Res Ctr, Manchester, Lancs, England
Cathryn Edwards - Torbay Hosp, Endoscopy Reg Training Unit, Torquay, England
Tariq Ahmad - Phillips Exeter Academy
John C. Mansfield - Newcastle University
Jack Satsangi - University of Edinburgh
Miles Parkes - Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge, England
Christopher G. Mathew - Supreme Council Of Health
Peter Donnelly - Wellcome Trust
Leena Peltonen - Wellcome Sanger Institute
Jenefer M. Blackwell - College Station Medical Center
Elvira Bramon - College Station Medical Center
Matthew A. Brown - University of Queensland
Juan P. Casas - Supreme Council Of Health
Aiden Corvin - College Station Medical Center
Nicholas Craddock - Cardiff University
Panos Deloukas - Wellcome Sanger Institute
Audrey Duncanson - Wellcome Trust
Janusz Jankowski - Supreme Council Of Health
Hugh S. Markus - University of London
Mark I. McCarthy - Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab ICDEM, Oxford OX3 7LJ, England
Colin N. A. Palmer - University of Dundee
Robert Plomin - Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England
Anna Rautanen - Wellcome Trust
Stephen J. Sawcer - University of Cambridge
Nilesh Samani - University of Leicester
Richard C. Trembath - Supreme Council Of Health
Ananth C. Viswanathan - Moorfields Eye Hosp, NHS Fdn Trust, Glaucoma Res Unit, London, England
Nicholas Wood - Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Chris C. A. Spencer - Wellcome Trust
Celine Bellenguez - Wellcome Trust
Daniel Davison - University of Oxford
Colin Freeman - Wellcome Trust
Amy Strange - Wellcome Trust
Cordelia Langford - Wellcome Sanger Institute
Sarah E. Hunt - Wellcome Sanger Institute
Sarah Edkins - Wellcome Sanger Institute
Rhian Gwilliam - Wellcome Sanger Institute
Hannah Blackburn - Wellcome Sanger Institute
Suzannah J. Bumpstead - Wellcome Sanger Institute
Serge Dronov - Wellcome Sanger Institute
Matthew Gillman - Wellcome Sanger Institute
Emma Gray - Wellcome Sanger Institute
Naomi Hammond - Wellcome Sanger Institute
Alagurevathi Jayakumar - Wellcome Sanger Institute
Owen T. McCann - Wellcome Sanger Institute
Jennifer Liddle - Wellcome Sanger Institute
Marc L. Perez - Wellcome Sanger Institute
Simon C. Potter - Wellcome Sanger Institute
Radhi Ravindrarajah - Wellcome Sanger Institute
Michelle Ricketts - Wellcome Sanger Institute
Matthew Waller - Wellcome Sanger Institute
Paul Weston - Wellcome Sanger Institute
Sara Widaa - Wellcome Sanger Institute
Pamela Whittaker - Wellcome Sanger Institute
Antony P. Attwood - Wellcome Sanger Institute
Jonathan Stephens - University of Cambridge
Jennifer Sambrook - University of Cambridge
Willem H. Ouwehand - Wellcome Sanger Institute
Wendy L. McArdle - University of Bristol
Susan M. Ring - College Station Medical Center
David P. Strachan - George Institute for Global Health
1958 Birth Cohort Controls
Publication Details: Nature genetics, Vol.41(12), pp.1330-U99
Publisher: Springer Nature
Number of pages: 7
Grant note: Central Manchester NHS Foundation Trust in partnership with the University of Manchester Clinical Research Facility at the Peninsular College of Medicine and Dentistry, Exeter Torbay Hospital Medical Fund Department of Health via the National Institute for Health Research (NIHR); National Institutes of Health Research (NIHR) 083948/Z/07/Z; 068545/Z/02 / Wellcome Trust G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); Spanish Government G0800759; G0800509; G0800383; G19/2; G0000934; G0600329; G0800675; MC_qA137934; G0601387 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Wolfson-Royal Society Merit Award; Royal Society Special Trustees of Moorfields National Health Service (NHS) Foundation Trust CZB/4/540 / Chief Scientist Office Guy's and St. Thomas' Charity NF-SI-0507-10379; PDA/02/06/016 / National Institute for Health Research; National Institutes of Health Research (NIHR) G0601387 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0600329; G0800675; G0800759; G0601387; MC_qA137934; G0800383; G0800509; G0000934; G9817803B; G19/2 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Evelyn Trust Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Cambridge University Hospitals NHS Foundation National Association for Colitis and Crohn's Disease (NACC) Moorfields Eye Hospital in partnership with University College London Institute of Ophthalmology
Identifiers: 9926138308331
Academic Unit: Prince Sattam Bin Abdulaziz University; King Abdulaziz University
Language: English
Resource Type: Journal article