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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-04

AUTHORS

The Wellcome Trust Case Control Consortium, 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, Inês 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

ABSTRACT

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 approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 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. More... »

PAGES

713

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  • Journal

    TITLE

    Nature

    ISSUE

    7289

    VOLUME

    464

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08979

    DOI

    http://dx.doi.org/10.1038/nature08979

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1003788883

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20360734


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