Key result
A bivariate genome-wide association scan discovered six novel genetic loci individually associated with both lipid levels and coronary artery disease.
Why the study?
GWAS routinely analyze plasma lipid levels and CAD independently, whereas joint GWAS for two related phenotypes can increase power to detect variants contributing to both traits.
Observational (n=735,838)
Yes
A bivariate genome-wide association study identified six novel genetic loci associated with both lipid levels and coronary artery disease, suggesting shared regulatory mechanisms.
Novel lipid-CAD loci support pleiotropy; leaves open validation for risk prediction or target discovery.
BACKGROUND: Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independent of one another. Joint GWAS for two related phenotypes can lead to a higher powered analysis to detect variants contributing to both traits. METHODS: We performed a bivariate GWAS to discover novel loci associated with both heart disease, using a CAD meta-analysis (122 733 cases and 424 528 controls), and lipid traits, using results from the Global Lipid Genetics Consortium (188 577 subjects). RESULTS: ), three which were associated with triglycerides and CAD, two which were associated with LDL (low-density lipoprotein) cholesterol and CAD, and one associated with total cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for more than one neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity. CONCLUSIONS: We discovered six novel variants individually associated with both lipids and CAD.
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Siewert et al. (2018) conducted an observational in Coronary Artery Disease and Lipid Levels (n=735,838). Genetic variants (novel loci) was evaluated on Association with both coronary artery disease and lipid traits. A bivariate genome-wide association scan discovered six novel genetic loci individually associated with both lipid levels and coronary artery disease.
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