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, Brown, Matthew A. and The Wellcome Trust Case Control Consortium (2010) Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature, 464 7289: 713-720. doi:10.1038/nature08979

Author Craddock, Nick
Hurles, Matthew E.
Cardin, Niall
Pearson, Richard D.
Plagnol, Vincent
Robson, Samuel
Vukcevic, Damjan
Barnes, Chris
Brown, Matthew A.
The Wellcome Trust Case Control Consortium
Title Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2010-04-01
Sub-type Article (original research)
DOI 10.1038/nature08979
Volume 464
Issue 7289
Start page 713
End page 720
Total pages 8
Place of publication London , United Kingdom
Publisher Nature Publishing Group
Collection year 2011
Language eng
Subject 060407 Genome Structure and Regulation
0604 Genetics
Formatted 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. © 2010 Macmillan Publishers Limited. All rights reserved.
Keyword Copy-number variation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
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Created: Sun, 11 Apr 2010, 00:02:13 EST