Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Nick Craddock; Matthew E. Hurles; Niall Cardin; Richard D. Pearson; Vincent Plagnol; Samuel Robson; Damjan Vukcevic; Chris Barnes; Donald F. Conrad; Eleni Giannoulatou; Chris Holmes; Jonathan L. Marchini; Kathy Stirrups; Martin D. Tobin; Louise V. Wain; Chris Yau; Jan Aerts; Tariq Ahmad; T. Daniel Andrews; Hazel Arbury; Anthony Attwood; Adam Auton; Stephen G. Ball; Anthony J. Balmforth; Jeffrey C. Barrett; Ines Barroso; Anne Barton; Amanda J. Bennett; Sanjeev Bhaskar; Katarzyna Blaszczyk; John Bowes; Oliver J. Brand; Peter S. Braund; Francesca Bredin; Gerome Breen; Morris J. Brown; Ian N. Bruce; Jaswinder Bull; Oliver S. Burren; John Burton; Jake Byrnes; Sian Caesar; Chris M. Clee; Alison J. Coffey; John M. C. Connell; Jason D. Cooper; Anna F. Dominiczak; Kate Downes; Hazel E. Drummond; Darshna Dudakia; Andrew Dunham; Bernadette Ebbs; Diana Eccles; Sarah Edkins; Cathryn Edwards; Anna Elliot; Paul Emery; David M. Evans; Gareth Evans; Steve Eyre; Anne Farmer; I. Nicol Ferrier; Lars Feuk; Tomas Fitzgerald; Edward Flynn; Alistair Forbes; Liz Forty; Jayne A. Franklyn; Rachel M. Freathy; Polly Gibbs; Paul Gilbert; Omer Gokumen; Katherine Gordon-Smith; Emma Gray; Elaine Green; Chris J. Groves; Detelina Grozeva; Rhian Gwilliam; Anita Hall; Naomi Hammond; Matt Hardy; Pile Harrison; Neelam Hassanali; Husam Hebaishi; Sarah Hines; Anne Hinks; Graham A. Hitman; Lynne Hocking; Eleanor Howard; Philip Howard; Joanna M. M. Howson; Debbie Hughes; Sarah Hunt; John D. Isaacs; Mahim Jain; Derek P. Jewell; Toby Johnson; Jennifer D. Jolley; Ian R. Jones; Lisa A. Jones; George Kirov; Cordelia F. Langford; Hana Lango-Allen; G. Mark Lathrop; James Lee; Kate L. Lee; Charlie Lees; Kevin Lewis; Cecilia M. Lindgren; Meeta Maisuria-Armer; Julian Maller; John Mansfield; Paul Martin; Dunecan C. O. Massey; Wendy L. McArdle; Peter McGuffin; Kirsten E. McLay; Alex Mentzer; Michael L. Mimmack; Ann E. Morgan; Andrew P. Morris; Craig Mowat; Simon Myers; William Newman; Elaine R. Nimmo; Michael C. O'Donovan; Abiodun Onipinla; Ifejinelo Onyiah; Nigel R. Ovington; Michael J. Owen; Kimmo Palin; Kirstie Parnell; David Pernet; John R. B. Perry; Anne Phillips; Dalila Pinto; Natalie J. Prescott; Inga Prokopenko; Michael A. Quail; Suzanne Rafelt; Nigel W. Rayner; Richard Redon; David M. Reid; Anthony Renwick; Susan M. Ring; Neil Robertson; Ellie Russell; David St Clair; Jennifer G. Sambrook; Jeremy D. Sanderson; Helen Schuilenburg; Carol E. Scott; Richard Scott; Sheila Seal; Sue Shaw-Hawkins; Beverley M. Shields; Matthew J. Simmonds; Debbie J. Smyth; Elilan Somaskantharajah; Katarina Spanova; Sophia Steer; Jonathan Stephens; Helen E. Stevens; Millicent A. Stone; Zhan Su; Deborah P. M. Symmons; John R. Thompson; Wendy Thomson; Mary E. Travers; Clare Turnbull; Armand Valsesia; Mark Walker; Neil M. Walker; Chris Wallace; Margaret Warren-Perry; Nicholas A. Watkins; John Webster; Michael N. Weedon; Anthony G. Wilson; Matthew Woodburn; B. Paul Wordsworth; Allan H. Young; Eleftheria Zeggini; Nigel P. Carter; Timothy M. Frayling; Charles Lee; Gil McVean; Patricia B. Munroe; Aarno Palotie; Stephen J. Sawcer; Stephen W. Scherer; David P. Strachan; Chris Tyler-Smith; Matthew A. Brown; Paul R. Burton; Mark J. Caulfield; Alastair Compston; Martin Farrall; Stephen C. L. Gough; Alistair S. Hall; Andrew T. Hattersley; Adrian V. S. Hill; Christopher G. Mathew; Marcus Pembrey; Jack Satsangi; Michael R. Stratton; Jane Worthington; Panos Deloukas; Audrey Duncanson; Dominic P. Kwiatkowski; Mark I. McCarthy; Willem H. Ouwehand; Miles Parkes; Nazneen Rahman; John A. Todd; Nilesh J. Samani; Peter Donnelly; Wellcome Trust Case Control

doi:10.1038/nature08979

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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Nick Craddock, Matthew E. Hurles, Niall Cardin, Richard D. Pearson, Vincent Plagnol, Samuel Robson, Damjan Vukcevic, Chris Barnes, Donald F. Conrad, Eleni Giannoulatou, …

Nature (London), Vol.464(7289), pp.713-U86

01/04/2010

DOI: https://doi.org/10.1038/nature08979

PMID: 20360734

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

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Title: Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
Creators - without role: Nick Craddock - Cardiff University
Matthew E. Hurles - Wellcome Sanger Institute
Niall Cardin - University of Oxford
Richard D. Pearson - University of Oxford
Vincent Plagnol - University of Cambridge
Samuel Robson - Wellcome Sanger Institute
Damjan Vukcevic - University of Oxford
Chris Barnes - Wellcome Sanger Institute
Donald F. Conrad - Wellcome Sanger Institute
Eleni Giannoulatou - University of Oxford
Chris Holmes - University of Oxford
Jonathan L. Marchini - University of Oxford
Kathy Stirrups - Wellcome Sanger Institute
Martin D. Tobin - University of Leicester
Louise V. Wain - University of Leicester
Chris Yau - University of Oxford
Jan Aerts - Wellcome Sanger Institute
Tariq Ahmad - University of Exeter
T. Daniel Andrews - Wellcome Sanger Institute
Hazel Arbury - Wellcome Sanger Institute
Anthony Attwood - Wellcome Sanger Institute
Adam Auton - University of Oxford
Stephen G. Ball - University of Leeds
Anthony J. Balmforth - University of Leeds
Jeffrey C. Barrett - Wellcome Sanger Institute
Ines Barroso - Wellcome Sanger Institute
Anne Barton - University of Manchester
Amanda J. Bennett - University of Oxford
Sanjeev Bhaskar - Wellcome Sanger Institute
Katarzyna Blaszczyk - Supreme Council Of Health
John Bowes - University of Manchester
Oliver J. Brand - University of Birmingham
Peter S. Braund - University of Leicester
Francesca Bredin - Addenbrookes Hosp, IBD Genet Res Grp, Cambridge CB2 0QQ, England
Gerome Breen - University of Aberdeen
Morris J. Brown - University of Cambridge
Ian N. Bruce - University of Manchester
Jaswinder Bull - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Oliver S. Burren - University of Cambridge
John Burton - Wellcome Sanger Institute
Jake Byrnes - University of Oxford
Sian Caesar - University of Birmingham
Chris M. Clee - Wellcome Sanger Institute
Alison J. Coffey - Wellcome Sanger Institute
John M. C. Connell - University of Glasgow
Jason D. Cooper - University of Cambridge
Anna F. Dominiczak - University of Glasgow
Kate Downes - University of Cambridge
Hazel E. Drummond - University of Edinburgh
Darshna Dudakia - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Andrew Dunham - Wellcome Sanger Institute
Bernadette Ebbs - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Diana Eccles - University of Southampton
Sarah Edkins - Wellcome Sanger Institute
Cathryn Edwards - Torbay Hosp, Endoscopy Reg Training Unit, Torquay TQ2 7AA, England
Anna Elliot - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Paul Emery - University of Leeds
David M. Evans - University of Bristol
Gareth Evans - University of Manchester
Steve Eyre - University of Manchester
Anne Farmer - Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England
I. Nicol Ferrier - Supreme Council Of Health
Lars Feuk - Hosp Sick Children, MaRS Ctr, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada
Tomas Fitzgerald - Wellcome Sanger Institute
Edward Flynn - University of Manchester
Alistair Forbes - Univ Coll London Hosp Trust, Inst Digest Dis, London NW1 2BU, England
Liz Forty - Cardiff University
Jayne A. Franklyn - University of Birmingham
Rachel M. Freathy - University of Exeter
Polly Gibbs - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Paul Gilbert - University of Manchester
Omer Gokumen - Brigham and Women's Hospital
Katherine Gordon-Smith - University of Birmingham
Emma Gray - Wellcome Sanger Institute
Elaine Green - Cardiff University
Chris J. Groves - University of Oxford
Detelina Grozeva - Cardiff University
Rhian Gwilliam - Wellcome Sanger Institute
Anita Hall - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Naomi Hammond - Wellcome Sanger Institute
Matt Hardy - University of Cambridge
Pile Harrison - University of Oxford
Neelam Hassanali - University of Oxford
Husam Hebaishi - Wellcome Sanger Institute
Sarah Hines - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Anne Hinks - University of Manchester
Graham A. Hitman - College Station Medical Center
Lynne Hocking - University of Aberdeen
Eleanor Howard - Wellcome Sanger Institute
Philip Howard - Queen Mary University of London
Joanna M. M. Howson - University of Cambridge
Debbie Hughes - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Sarah Hunt - Wellcome Sanger Institute
John D. Isaacs - Supreme Council Of Health
Mahim Jain - University of Oxford
Derek P. Jewell - University of Oxford
Toby Johnson - Queen Mary University of London
Jennifer D. Jolley - University of Cambridge
Ian R. Jones - Cardiff University
Lisa A. Jones - University of Birmingham
George Kirov - Cardiff University
Cordelia F. Langford - Wellcome Sanger Institute
Hana Lango-Allen - University of Exeter
G. Mark Lathrop - Ctr Natl Genotypage, F-91057 Paris, France
James Lee - Addenbrookes Hosp, IBD Genet Res Grp, Cambridge CB2 0QQ, England
Kate L. Lee - Queen Mary University of London
Charlie Lees - University of Edinburgh
Kevin Lewis - Wellcome Sanger Institute
Cecilia M. Lindgren - University of Oxford
Meeta Maisuria-Armer - University of Cambridge
Julian Maller - University of Oxford
John Mansfield - Newcastle University
Paul Martin - University of Manchester
Dunecan C. O. Massey - Addenbrookes Hosp, IBD Genet Res Grp, Cambridge CB2 0QQ, England
Wendy L. McArdle - University of Bristol
Peter McGuffin - Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England
Kirsten E. McLay - Wellcome Sanger Institute
Alex Mentzer - Supreme Council Of Health
Michael L. Mimmack - Wellcome Sanger Institute
Ann E. Morgan - University of Leeds
Andrew P. Morris - University of Oxford
Craig Mowat - University of Dundee
Simon Myers - University of Oxford
William Newman - University of Manchester
Elaine R. Nimmo - University of Edinburgh
Michael C. O'Donovan - Cardiff University
Abiodun Onipinla - Queen Mary University of London
Ifejinelo Onyiah - Wellcome Sanger Institute
Nigel R. Ovington - University of Cambridge
Michael J. Owen - Cardiff University
Kimmo Palin - Wellcome Sanger Institute
Kirstie Parnell - University of Exeter
David Pernet - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
John R. B. Perry - University of Exeter
Anne Phillips - University of Dundee
Dalila Pinto - Hosp Sick Children, MaRS Ctr, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada
Natalie J. Prescott - Supreme Council Of Health
Inga Prokopenko - University of Oxford
Michael A. Quail - Wellcome Sanger Institute
Suzanne Rafelt - University of Leicester
Nigel W. Rayner - University of Oxford
Richard Redon - Wellcome Sanger Institute
David M. Reid - University of Aberdeen
Anthony Renwick - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Susan M. Ring - University of Bristol
Neil Robertson - University of Oxford
Ellie Russell - Cardiff University
David St Clair - University of Aberdeen
Jennifer G. Sambrook - University of Cambridge
Jeremy D. Sanderson - Supreme Council Of Health
Helen Schuilenburg - University of Cambridge
Carol E. Scott - Wellcome Sanger Institute
Richard Scott - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Sheila Seal - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Sue Shaw-Hawkins - Queen Mary University of London
Beverley M. Shields - University of Exeter
Matthew J. Simmonds - University of Birmingham
Debbie J. Smyth - University of Cambridge
Elilan Somaskantharajah - Wellcome Sanger Institute
Katarina Spanova - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Sophia Steer - Kings Coll Hosp Natl Hlth Serv Fdn Trust, London SE5 9RS, England
Jonathan Stephens - University of Cambridge
Helen E. Stevens - University of Cambridge
Millicent A. Stone - University of Toronto
Zhan Su - University of Oxford
Deborah P. M. Symmons - University of Manchester
John R. Thompson - University of Leicester
Wendy Thomson - University of Manchester
Mary E. Travers - University of Oxford
Clare Turnbull - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Armand Valsesia - Wellcome Sanger Institute
Mark Walker - Newcastle Univ, Diabet Res Grp, Sch Clin Med Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
Neil M. Walker - University of Cambridge
Chris Wallace - University of Cambridge
Margaret Warren-Perry - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
Nicholas A. Watkins - University of Cambridge
John Webster - Aberdeen Royal Infirm, Aberdeen AB9 2ZB, Grampian, Scotland
Michael N. Weedon - University of Exeter
Anthony G. Wilson - University of Sheffield
Matthew Woodburn - University of Cambridge
B. Paul Wordsworth - University of Oxford
Allan H. Young - Supreme Council Of Health
Eleftheria Zeggini - Wellcome Sanger Institute
Nigel P. Carter - Wellcome Sanger Institute
Timothy M. Frayling - University of Exeter
Charles Lee - Brigham and Women's Hospital
Gil McVean - University of Oxford
Patricia B. Munroe - Queen Mary University of London
Aarno Palotie - Wellcome Sanger Institute
Stephen J. Sawcer - University of Cambridge
Stephen W. Scherer - Hosp Sick Children, MaRS Ctr, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada
David P. Strachan - University of London
Chris Tyler-Smith - Wellcome Sanger Institute
Matthew A. Brown - University of Oxford
Paul R. Burton - University of Leicester
Mark J. Caulfield - Queen Mary University of London
Alastair Compston - University of Cambridge
Martin Farrall - University of Oxford
Stephen C. L. Gough - University of Birmingham
Alistair S. Hall - University of Leeds
Andrew T. Hattersley - University of Exeter
Adrian V. S. Hill - University of Oxford
Christopher G. Mathew - Supreme Council Of Health
Marcus Pembrey - UCL, Inst Child Hlth, Clin & Mol Genet Unit, London WC1N 1EH, England
Jack Satsangi - University of Edinburgh
Michael R. Stratton - Wellcome Sanger Institute
Jane Worthington - University of Manchester
Panos Deloukas - Wellcome Sanger Institute
Audrey Duncanson - Wellcome Trust
Dominic P. Kwiatkowski - Wellcome Sanger Institute
Mark I. McCarthy - University of Oxford
Willem H. Ouwehand - Wellcome Sanger Institute
Miles Parkes - Addenbrookes Hosp, IBD Genet Res Grp, Cambridge CB2 0QQ, England
Nazneen Rahman - Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England
John A. Todd - University of Cambridge
Nilesh J. Samani - University of Leicester
Peter Donnelly - University of Oxford
Wellcome Trust Case Control
Publication Details: Nature (London), Vol.464(7289), pp.713-U86
Publisher: NATURE PORTFOLIO
Number of pages: 10
Grant note: Wellcome Trust; European Commission G0800675 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 18475 / Versus Arthritis RG/08/014/24067 / British Heart Foundation NF-SI-0508-10335 / National Institute for Health Research; National Institute for Health Research (NIHR) G9817803B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission CZB/4/540 / Chief Scientist Office
Identifiers: 9925566508331
Academic Unit: Prince Sattam Bin Abdulaziz University; King Abdulaziz University
Language: English
Resource Type: Journal article