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

Craddock, Nick, Hurles, Matthew E., Cardin, Niall , Pearson, Richard D., Plagnol, Vincent, Robson, Samuel, Vukcevic, Damjan, Barnes, Chris, Conrad, Donald F., Giannoulatou, Eleni, Holmes, Chris, Marchini, Jonathan L., Stirrups, Kathy, Tobin, Martin D., Wain, Louise V., Yau, Chris, Aerts, Jan, Ahmad, Tariq, Daniel Andrews, T., Arbury, Hazel, Attwood, Anthony, Auton, Adam, Ball, Stephen G., Balmforth, Anthony J., Barrett, Jeffrey C., Barroso, Inês, Barton, Anne, Bennett, Amanda J., Bhaskar, Sanjeev, Blaszczyk, Katarzyna, Bowes, John, Brand, Oliver J., Braund, Peter S., Bredin, Francesca, Breen, Gerome, Brown, Morris J., Bruce, Ian N., Bull, Jaswinder, Burren, Oliver S., Burton, John, Byrnes, Jake, Caesar, Sian, Clee, Chris M., Coffey, Alison J., Connell, John M. C., Cooper, Jason D., Dominiczak, Anna F., Downes, Kate, Drummond, Hazel E., Dudakia, Darshna, Dunham, Andrew, Ebbs, Bernadette, Eccles, Diana, Edkins, Sarah, Edwards, Cathryn, Elliot, Anna, Emery, Paul, Evans, David M., Evans, Gareth, Eyre, Steve, Farmer, Anne, Nicol Ferrier, I., Feuk, Lars, Fitzgerald, Tomas, Flynn, Edward, Forbes, Alistair, Forty, Liz, Franklyn, Jayne A., Freathy, Rachel M., Gibbs, Polly, Gilbert, Paul, Gokumen, Omer, Gordon-Smith, Katherine, Gray, Emma, Green, Elaine, Groves, Chris J., Grozeva, Detelina, Gwilliam, Rhian, Hall, Anita, Hammond, Naomi, Hardy, Matt, Harrison, Pile, Hassanali, Neelam, Hebaishi, Husam, Hines, Sarah, Hinks, Anne, Hitman, Graham A, Hocking, Lynne, Howard, Eleanor, Howard, Philip, Howson, Joanna M. M., Hughes, Debbie, Hunt, Sarah, Isaacs, John D., Jain, Mahim, Jewell, Derek P., Johnson, Toby, Jolley, Jennifer D., Jones, Ian R., Jones, Lisa A., Kirov, George, Langford, Cordelia F., Lango-Allen, Hana, Mark Lathrop, G., Lee, James, Lee, Kate L., Lees, Charlie, Lewis, Kevin, Lindgren, Cecilia M., Maisuria-Armer, Meeta, Maller, Julian, Mansfield, John, Martin, Paul, Massey, Dunecan C. O., McArdle, Wendy L., McGuffin, Peter, McLay, Kirsten E., Mentzer, Alex, Mimmack, Michael L., Morgan, Ann E., Morris, Andrew P., Mowat, Craig, Myers, Simon, Newman, William, Nimmo, Elaine R., O’Donovan, Michael C., Onipinla, Abiodun, Onyiah, Ifejinelo, Ovington, Nigel R., Owen, Michael J., Palin, Kimmo, Parnell, Kirstie, Pernet, David, Perry, John R. B., Phillips, Anne, Pinto, Dalila, Prescott, Natalie J., Prokopenko, Inga, Quail, Michael A., Rafelt, Suzanne, Rayner, Nigel W., Redon, Richard, Reid, David M., Renwick, Anthony, Ring, Susan M., Robertson, Neil, Russell, Ellie, St Clair, David, Sambrook, Jennifer G., Sanderson, Jeremy D., Schuilenburg, Helen, Scott, Carol E., Scott, Richard, Seal, Sheila, Shaw-Hawkins, Sue, Shields, Beverley M., Simmonds, Matthew J., Smyth, Debbie J., Somaskantharajah, Elilan, Spanova, Katarina, Steer, Sophia, Stephens, Jonathan, Stevens, Helen E., Stone, Millicent A., Su, Zhan, Symmons, Deborah P. M., Thompson, John R., Thomson, Wendy, Travers, Mary E., Turnbull, Clare, Valsesia, Armand, Walker, Mark, Walker, Neil M., Wallace, Chris, Warren-Perry, Margaret, Watkins, Nicholas A., Webster, John, Weedon, Michael N., Wilson, Anthony G., Woodburn, Matthew, Wordsworth, B. Paul, Young, Allan H., Zeggini, Eleftheria, Carter, Nigel P., Frayling, Timothy M., Lee, Charles, McVean, Gil, Munroe, Patricia B., Palotie, Aarno, Sawcer, Stephen J., Scherer, Stephen W., Strachan, David P., Tyler-Smith, Chris, Brown, Matthew A., Burton, Paul R., Caulfield, Mark J., Compston, Alastair, Farrall, Martin, Gough, Stephen C. L., Hall, Alistair S., Hattersley, Andrew T., Hill, Adrian V. S., Mathew, Christopher G., Pembrey, Marcus, Satsangi, Jack, Stratton, Michael R., Worthington, Jane, Deloukas, Panos, Duncanson, Audrey, Kwiatkowski, Dominic P., McCarthy, Mark I., Ouwehand, Willem H., Parkes, Miles, Rahman, Nazneen, Todd, John A., Samani, Nilesh J. and Donnelly, Peter (2010) Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature, 464 (7289). pp. 713-720. ISSN 0028-0836

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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 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 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 diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough 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. © 2010 Macmillan Publishers Limited. All rights reserved.

Additional Information:The Wellcome Trust Case Control Consortium
Keywords:genetics, copy number variants, Common disease, single nucleotide polymorphism
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:23670
Deposited On:01 Aug 2016 13:54

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