studies Study Report - GWAS of coronary artery disease in a British population (HGVST11)
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Identifier HGVST11
Study name GWAS of coronary artery disease in a British population
Total p-values imported 63
Phenotype(s) tested
Coronary artery disease
Study design Case and control
Genotype platforms Affymetrix 500K Gene Chip
Abstract Summary-level data and analysis results of Coronary Artery Disease (CAD) imported from the Wellcome Trust Case Control Consortium project
Submission information
ContributorDate
Submitted		 Author? Submitter? Source?
WTCCC1 2009-03-30 yes no yes
HGVbaseG2P 2009-03-30 no yes no
Author communication info
Corresponding author Date of contact Response received Date of response Type of response info
Peter Donnelly 2011-03-17 no -- --
2012-01-18 no -- --
Related links WTCCC1link
Background The Wellcome Trust Case Control Consortium (WTCCC) was formed with a view to exploring the utility, design and analyses of GWA studies. It brought together over 50 research groups from the UK that are active in researching the genetics of common human diseases, with expertise ranging from clinical, through genotyping, to informatics and statistical analysis. Coronary artery disease (coronary atherosclerosis) is a chronic degenerative condition in which lipid and fibrous matrix is deposited in the walls of the coronary arteries to form atheromatous plaques. It may be clinically silent or present with angina pectoris or acute myocardial infarction. Pathogenesis is complex, with endothelial dysfunction, oxidative stress and inflammation contributing to development and instability of the atherosclerotic plaque.In addition to lifestyle and environmental factors, genes are important in the aetiology of CAD.  
Objectives The main experiment consisted of a GWA study of 2,000 cases and 3,000 shared controls for a complex human disease of major public health importance, Coronary Artery Disease (CAD). By simultaneously studying Crohn's Disease (CD) with other diseases with differing aetiologies, we hoped to develop in sights, not only into the specific genetic contributions to each of the diseases, but also into differences in allelic architecture across the diseases. A further major aim was to address important methodological issues of relevance to all GWA studies, such as quality control, design and analysis. In addition to our main association results, we address several of these issues below, including the choice of controls for genetic studies, the extent of population structure within Great Britain, sample sizes necessary to detect genetic effects of varying sizes, and improvements in genotype-calling algorithms and analytical methods.
Key results The most notable new finding for CAD is the powerful association on chromosome 9p21.3. Although the strongest signal is seen at rs1333049 (P = 1.8x10-14), associations are seen for SNPs across > 100 kilobases. A potentially interesting association is at rs6922269 (P = 6.3x10-6), an intronic SNP in MTHFD1L, which encodes methylenetetrahydrofolate dehydrogenase (NADP+-dependent) 1-like, the mitochondrial isozyme of C1-tetrahydrofolate (THF) synthase An intronic SNP in ADAMTS17 (a disintegrin and metalloproteinase with thrombospondin motifs 17), which showed modest association (rs1994016; P = 1.1 10-4) in our primary analysis, showed a much stronger association in the expanded reference group analysis
Conclusions Not supplied
Reason for study size Not supplied
Study power Not supplied
Sources of bias Not supplied
Limitations Not supplied
Acknowledgements The principal funder of this project was the Wellcome Trust. Please see publication for the full list of acknowledgements.
Related citations
The Wellcome Trust Case Control Consortiumlink
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
Nature 2007 Jun 7;447(7145):661-78