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

Nature volume 464, pages 713–720 (2010)Cite this article

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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 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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Figure 1: Flowchart showing which CNVs are included on the array.
Figure 2: Illustrative CNVs.
Figure 3: Genome-wide association results.

References

  1. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009)

    Article  CAS  ADS  Google Scholar 

  2. Zhang, F., Gu, W., Hurles, M. E. & Lupski, J. R. Copy number variation in human health, disease, and evolution. Annu. Rev. Genomics Hum. Genet. 10, 451–481 (2009)

    Article  CAS  Google Scholar 

  3. Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007)

    Article  CAS  ADS  Google Scholar 

  4. Stankiewicz, P. & Beaudet, A. L. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr. Opin. Genet. Dev. 17, 182–192 (2007)

    Article  CAS  Google Scholar 

  5. Stefansson, H. et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236 (2008)

    Article  CAS  ADS  Google Scholar 

  6. The International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237–241 (2008)

  7. McCarroll, S. A. et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nature Genet. 40, 1107–1112 (2008)

    Article  CAS  Google Scholar 

  8. Willer, C. J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genet. 41, 25–34 (2009)

    Article  CAS  Google Scholar 

  9. de Cid, R. et al. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nature Genet. 41, 211–215 (2009)

    Article  CAS  Google Scholar 

  10. Hollox, E. J. et al. Psoriasis is associated with increased β-defensin genomic copy number. Nature Genet. 40, 23–25 (2008)

    Article  CAS  Google Scholar 

  11. Diskin, S. J. et al. Copy number variation at 1q21.1 associated with neuroblastoma. Nature 459, 987–991 (2009)

    Article  CAS  ADS  Google Scholar 

  12. Conrad, D. F. et al. Origins and functional impact of copy number variation in the human genome. Nature 10.1038/nature08516 (7 October 2009)

  13. Murray, C. J. & Lopez, A. D. Evidence-based health policy–lessons from the Global Burden of Disease Study. Science 274, 740–743 (1996)

    Article  CAS  ADS  Google Scholar 

  14. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007)

  15. McCarroll, S. A. & Altshuler, D. M. Copy-number variation and association studies of human disease. Nature Genet. 39, S37–S42 (2007)

    Article  CAS  Google Scholar 

  16. Locke, D. P. et al. Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. Am. J. Hum. Genet. 79, 275–290 (2006)

    Article  CAS  Google Scholar 

  17. McCarroll, S. A. et al. Common deletion polymorphisms in the human genome. Nature Genet. 38, 86–92 (2006)

    Article  CAS  Google Scholar 

  18. Barnes, C. et al. A robust statistical method for case-control association testing with copy number variation. Nature Genet. 40, 1245–1252 (2008)

    Article  CAS  Google Scholar 

  19. Horton, R. et al. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics 60, 1–18 (2008)

    Article  CAS  Google Scholar 

  20. Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genet. 40, 638–645 (2008)

    Article  CAS  Google Scholar 

  21. Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet. 37, 129–137 (2005)

    Article  CAS  Google Scholar 

  22. Fanciulli, M. et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nature Genet. 39, 721–723 (2007)

    Article  CAS  Google Scholar 

  23. Mamtani, M. et al. CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Ann. Rheum. Dis. 67, 1076–1083 (2008)

    Article  CAS  Google Scholar 

  24. McKinney, C. et al. Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Ann. Rheum. Dis. 67, 409–413 (2008)

    Article  CAS  Google Scholar 

  25. Wilcoxon, F. Individual comparisons by ranking methods. Biom. Bull. 1, 80–83 (1945)

    Article  Google Scholar 

  26. Clayton, D. G. et al. Population structure, differential bias and genomic control in a large-scale, case-control association study. Nature Genet. 37, 1243–1246 (2005)

    Article  CAS  Google Scholar 

  27. Field, S. F. et al. Experimental aspects of copy number variant assays at CCL3L1. Nature Med. 15, 1115–1117 (2009)

    Article  CAS  Google Scholar 

  28. Lieber, M. R., Yu, K. & Raghavan, S. C. Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations. DNA Repair 5, 1234–1245 (2006)

    Article  CAS  Google Scholar 

  29. International HapMap Project. 〈http://hapmap.ncbi.nlm.nih.gov/〉 (2010)

  30. Redon, R. et al. Global variation in copy number in the human genome. Nature 444, 444–454 (2006)

    Article  CAS  ADS  Google Scholar 

  31. Levy, S. et al. The diploid genome sequence of an individual human. PLoS Biol. 5, e254 (2007)

    Article  Google Scholar 

  32. Kidd, J. M. et al. Mapping and sequencing of structural variation from eight human genomes. Nature 453, 56–64 (2008)

    Article  CAS  ADS  Google Scholar 

  33. McCarroll, S. A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nature Genet. 40, 1166–1174 (2008)

    Article  CAS  Google Scholar 

  34. Koch, S. et al. Association of multiple sclerosis with ILT6 deficiency. Genes Immun. 6, 445–447 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The principal funder of this project was the Wellcome Trust. Many individuals, groups, consortia, organizations and funding bodies have made important contributions to sample collections and coordination of the scientific analyses. Details are provided in Supplementary Information Section 11. We are indebted to all those who participated within the sample collections.

Author Contributions are listed in Supplementary Information.

Author information

Author notes

  1. Nick Craddock and Matthew E. Hurles: These authors contributed equally to this work.

Authors and Affiliations

  1. MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.,

    Nick Craddock, Liz Forty, Katherine Gordon-Smith, Elaine Green, Detelina Grozeva, Ian R. Jones, George Kirov, Michael C. O’Donovan, Michael J. Owen & Ellie Russell

  2. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.,

    Matthew E. Hurles, Samuel Robson, Chris Barnes, Donald F. Conrad, Kathy Stirrups, Jan Aerts, T. Daniel Andrews, Hazel Arbury, Anthony Attwood, Jeffrey C. Barrett, Inês Barroso, Sanjeev Bhaskar, John Burton, Chris M. Clee, Alison J. Coffey, Andrew Dunham, Sarah Edkins, Tomas Fitzgerald, Emma Gray, Rhian Gwilliam, Naomi Hammond, Husam Hebaishi, Eleanor Howard, Sarah Hunt, Cordelia F. Langford, Kevin Lewis, Kirsten E. McLay, Michael L. Mimmack, Ifejinelo Onyiah, Kimmo Palin, Michael A. Quail, Richard Redon, Carol E. Scott, Elilan Somaskantharajah, Armand Valsesia, Eleftheria Zeggini, Nigel P. Carter, Aarno Palotie, Chris Tyler-Smith, Michael R. Stratton, Panos Deloukas, Dominic P. Kwiatkowski & Willem H. Ouwehand

  3. Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.,

    Niall Cardin, Eleni Giannoulatou, Chris Holmes, Jonathan L. Marchini, Chris Yau, Adam Auton, Simon Myers, Zhan Su, Gil McVean & Peter Donnelly

  4. The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.,

    Richard D. Pearson, Damjan Vukcevic, Jake Byrnes, Mahim Jain, Cecilia M. Lindgren, Julian Maller, Andrew P. Morris, Inga Prokopenko, Nigel W. Rayner, Neil Robertson, Eleftheria Zeggini, Adrian V. S. Hill, Dominic P. Kwiatkowski, Mark I. McCarthy & Peter Donnelly

  5. Department of Medical Genetics, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.,

    Vincent Plagnol, Oliver S. Burren, Jason D. Cooper, Kate Downes, Matt Hardy, Joanna M. M. Howson, Meeta Maisuria-Armer, Nigel R. Ovington, Helen Schuilenburg, Debbie J. Smyth, Helen E. Stevens, Neil M. Walker, Chris Wallace, Matthew Woodburn & John A. Todd

  6. Departments of Health Sciences and Genetics, University of Leicester, 217 Adrian Building, University Road, Leicester LE1 7RH, UK.,

    Martin D. Tobin, Louise V. Wain, John R. Thompson & Paul R. Burton

  7. Genetics of Complex Traits, Peninsula College of Medicine and Dentistry University of Exeter, Exeter EX1 2LU, UK.,

    Tariq Ahmad

  8. Department of Haematology, University of Cambridge, Long Road, Cambridge CB2 0PT, UK.,

    Anthony Attwood, Jennifer D. Jolley, Jennifer G. Sambrook, Jonathan Stephens, Nicholas A. Watkins & Willem H. Ouwehand

  9. National Health Service Blood and Transplant, Cambridge Centre, Long Road, Cambridge CB2 0PT, UK.,

    Anthony Attwood, Jennifer D. Jolley, Jennifer G. Sambrook, Jonathan Stephens, Nicholas A. Watkins & Willem H. Ouwehand

  10. Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK.,

    Stephen G. Ball, Anthony J. Balmforth & Alistair S. Hall

  11. arc Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.,

    Anne Barton, John Bowes, Ian N. Bruce, Steve Eyre, Edward Flynn, Paul Gilbert, Anne Hinks, Paul Martin, Deborah P. M. Symmons, Wendy Thomson & Jane Worthington

  12. Oxford Centre for Diabetes, Endocrinology and Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.,

    Amanda J. Bennett, Chris J. Groves, Neelam Hassanali, Cecilia M. Lindgren, Inga Prokopenko, Nigel W. Rayner, Neil Robertson, Mary E. Travers & Mark I. McCarthy

  13. Department of Medical and Molecular Genetics, King’s College London School of Medicine, 8th Floor Guy’s Tower, Guy’s Hospital, London SE1 9RT, UK.,

    Katarzyna Blaszczyk, Natalie J. Prescott & Christopher G. Mathew

  14. Centre for Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.,

    Oliver J. Brand, Jayne A. Franklyn, Matthew J. Simmonds & Stephen C. L. Gough

  15. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.,

    Peter S. Braund, Suzanne Rafelt & Nilesh J. Samani

  16. IBD Genetics Research Group, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK.,

    Francesca Bredin, James Lee, Dunecan C. O. Massey & Miles Parkes

  17. University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.,

    Gerome Breen & David St Clair

  18. SGDP, The Institute of Psychiatry, King’s College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.,

    Gerome Breen, Anne Farmer & Peter McGuffin

  19. Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK.,

    Morris J. Brown

  20. Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, UK.,

    Jaswinder Bull, Darshna Dudakia, Bernadette Ebbs, Anna Elliot, Polly Gibbs, Anita Hall, Sarah Hines, Debbie Hughes, David Pernet, Anthony Renwick, Richard Scott, Sheila Seal, Katarina Spanova, Clare Turnbull, Margaret Warren-Perry, Michael R. Stratton & Nazneen Rahman

  21. Department of Psychiatry, University of Birmingham, National Centre for Mental Health, 25 Vincent Drive, Birmingham B15 2FG, UK.,

    Sian Caesar, Katherine Gordon-Smith & Lisa A. Jones

  22. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.,

    John M. C. Connell & Anna F. Dominiczak

  23. Division of Medical Sciences, Gastrointestinal Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.,

    Hazel E. Drummond, Charlie Lees, Elaine R. Nimmo & Jack Satsangi

  24. Academic Unit of Genetic Medicine, University of Southampton, Southampton SO16 5YA, UK.,

    Diana Eccles

  25. Endoscopy Regional Training Unit, Torbay Hospital, Torbay TQ2 7AA, UK.,

    Cathryn Edwards

  26. Academic Unit of Musculoskeletal Disease, University of Leeds, Chapel Allerton Hospital, Leeds, West Yorkshire LS7 4SA, UK.,

    Paul Emery

  27. Department of Social Medicine, MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol BS8 2BN, UK.,

    David M. Evans

  28. Department of Medical Genetics, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester M13 0JH, UK.,

    Gareth Evans & William Newman

  29. School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK.,

    I. Nicol Ferrier & Allan H. Young

  30. The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, MaRS Centre–East Tower, 101 College St, Room 14-701, Toronto, Ontario M5G 1L7, Canada.,

    Lars Feuk, Dalila Pinto & Stephen W. Scherer

  31. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden.,

    Lars Feuk

  32. Institute for Digestive Diseases, University College London Hospitals Trust, London NW1 2BU, UK.,

    Alistair Forbes

  33. University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK.,

    Jayne A. Franklyn & Stephen C. L. Gough

  34. Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter EX1 2LU, UK.,

    Rachel M. Freathy, Hana Lango-Allen, Kirstie Parnell, John R. B. Perry, Beverley M. Shields, Michael N. Weedon, Timothy M. Frayling & Andrew T. Hattersley

  35. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.,

    Omer Gokumen & Charles Lee

  36. University of Oxford, Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK.,

    Pile Harrison

  37. Centre for Diabetes and Metabolic Medicine, Barts and The London, Royal London Hospital, Whitechapel, London E1 1BB, UK.,

    Graham A Hitman

  38. Department of Medicine and Therapeutics, Bone Research Group, University of Aberdeen, Aberdeen AB25 2ZD, UK.,

    Lynne Hocking & David M. Reid

  39. Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.,

    Philip Howard, Toby Johnson, Kate L. Lee, Abiodun Onipinla, Sue Shaw-Hawkins, Patricia B. Munroe & Mark J. Caulfield

  40. Institute of Cellular Medicine, Musculoskeletal Research Group, 4th Floor, Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.,

    John D. Isaacs

  41. Gastroenterology Unit, Radcliffe Infirmary, University of Oxford, Oxford OX2 6HE, UK.,

    Derek P. Jewell

  42. Centre National de Genotypage, 2 Rue Gaston Cremieux, Evry, Paris 91057, France.,

    G. Mark Lathrop

  43. Department of Gastroenterology and Hepatology, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.,

    John Mansfield

  44. Department of Social Medicine, ALSPAC Laboratory, University of Bristol, Bristol BS8 2BN, UK.,

    Wendy L. McArdle & Susan M. Ring

  45. Division of Nutritional Sciences, King’s College London School of Biomedical and Health Sciences, London SE1 9NH, UK.,

    Alex Mentzer & Jeremy D. Sanderson

  46. NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds, West Yorkshire LS7 4SA, UK.,

    Ann E. Morgan

  47. Department of General Internal Medicine, Ninewells Hospital and Medical School, Ninewells Avenue, Dundee DD1 9SY, UK.,

    Craig Mowat & Anne Phillips

  48. INSERM UMR915, L’Institut du Thorax, Nantes 44035, France.,

    Richard Redon

  49. Clinical and Academic Rheumatology, Kings College Hospital National Health Service Foundation Trust, Denmark Hill, London SE5 9RS, UK.,

    Sophia Steer

  50. University of Toronto, St Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.,

    Millicent A. Stone

  51. University of Bath, Claverdon, Norwood House, Room 5.11a, Bath, Somerset BA2 7AY, UK.,

    Millicent A. Stone

  52. Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.,

    Mark Walker

  53. Medicine and Therapeutics, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Grampian AB9 2ZB, UK.,

    John Webster

  54. School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield S10 2JF, UK.,

    Anthony G. Wilson

  55. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of Oxford, Windmill Road, Headington, Oxford OX3 7LD, UK.,

    B. Paul Wordsworth & Matthew A. Brown

  56. UBC Institute of Mental Health, 430-5950 University Boulevard Vancouver, British Columbia V6T 1Z3, Canada.,

    Allan H. Young

  57. Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK.,

    Stephen J. Sawcer & Alastair Compston

  58. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.,

    Stephen W. Scherer

  59. Division of Community Health Sciences, St George’s, University of London, London SW17 0RE, UK.,

    David P. Strachan

  60. Diamantina Institute of Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, University of Queensland, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.,

    Matthew A. Brown

  61. Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.,

    Martin Farrall

  62. Genetics of Diabetes, Peninsula College of Medicine and Dentistry, University of Exeter, Barrack Road, Exeter EX2 5DW, UK.,

    Andrew T. Hattersley

  63. Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.,

    Marcus Pembrey

  64. The Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK.,

    Audrey Duncanson

  65. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LJ, UK.,

    Mark I. McCarthy

  66. Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK.,

    Nilesh J. Samani

Consortia

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

Corresponding author

Correspondence to Peter Donnelly.

Additional information

Summary information for the CNVs studied, including genomic locations, numbers of classes and SNP tags on different platforms is available at http://www.wtccc.org.uk/wtcccplus_cnv/supplemental.shtml. Full data are available, under a data access mechanism, from the European Genome-phenome Archive (http://www.ebi.ac.uk/ega/page.php).

Lists of authors and their affiliations appear at the end of the paper.

Supplementary information

Supplementary Information 1

This Supplementary Information file comprises: 1 Pilot study; 2 Samples; 3 CNV experiment, 4 Data and pre-processing; 5 Quality control procedures; 6 Calling and testing; 7 Properties of the CNV calls; 8 Replication and validation of associated CNVs in WTCCC; 9 Other analyses; 10 Glossary; 11 Acknowledgements; 12 Author contributions; 13 Supplementary Figures 1-33 with legends, 14 Tables 1-16 and Supplementary References. (PDF 10055 kb)

Supplementary Information 2

This file contains plots of CNV calls and association testing results produced by the CNVCALL/CNVTEST approach. (PDF 1196 kb)

Supplementary Information 3

This file contains plots of CNV calls and association testing results produced by the CNVtools approach. (PDF 756 kb)

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The Wellcome Trust Case Control Consortium. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature 464, 713–720 (2010). https://doi.org/10.1038/nature08979

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