Katherine M Siewert1, Benjamin F Voight2,3,4. 1. Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.M.S.). 2. Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (B.F.V.). 3. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (B.F.V.). 4. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (B.F.V.).
Abstract
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: We identified six previously unreported loci at genome-wide significance ( P<5×10-8), 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.
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: We identified six previously unreported loci at genome-wide significance ( P<5×10-8), 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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