Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

The Wellcome Trust Case Control Consortium, Bradbury, L. A. and Brown, M. A. (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447 7145: 661-678. doi:10.1038/nature05911

Author The Wellcome Trust Case Control Consortium
Bradbury, L. A.
Brown, M. A.
Title Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2007-06-07
Sub-type Article (original research)
DOI 10.1038/nature05911
Volume 447
Issue 7145
Start page 661
End page 678
Total pages 18
Editor P. Campbell
Place of publication United Kingdom
Publisher Nature Publishing Group
Collection year 2008
Language eng
Subject C1
270207 Quantitative Genetics
780105 Biological sciences
Abstract There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.
Keyword Multidisciplinary Sciences
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Matthew Brown and Linda Bradbury are both Diamantina Institute staff that are part of the Wellcome Trust Case Control Consortium (with Matt being a Primary Investigator) See hard copy version for verification and full listing. The total number of authors is 234

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4060 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 197 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 30 Apr 2008, 15:45:04 EST by Kylie Hengst on behalf of UQ Diamantina Institute