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 ArburyAnthony 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 Daniel 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, Lynne Hocking, David M Reid, David Malcolm St Clair, John Webster, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticlepeer-review

651 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)713-720
Number of pages8
Issue number7289
Publication statusPublished - 1 Apr 2010


  • Arthritis, Rheumatoid
  • Case-Control Studies
  • Crohn Disease
  • DNA Copy Number Variations
  • Diabetes Mellitus
  • Disease
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • Quality Control


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