Large-scale association analysis identifies new risk loci for coronary artery disease.
Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
Duke Scholars
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Related Subject Headings
- White People
- Risk Factors
- Quantitative Trait Loci
- Polymorphism, Single Nucleotide
- Middle Aged
- Male
- Humans
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Gene Regulatory Networks
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- White People
- Risk Factors
- Quantitative Trait Loci
- Polymorphism, Single Nucleotide
- Middle Aged
- Male
- Humans
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Gene Regulatory Networks