Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10−8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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We thank the Global Lipids Genetics Consortium for early access to the association results of the Metabochip study. S. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital, the Howard Goodman Fellowship from Massachusetts General Hospital, the Donovan Family Foundation, R01HL107816 from the US National Institutes of Health and a grant from Fondation Leducq. R.D. is supported by a Banting Fellowship from the Canadian Institutes of Health Research. G.P. is supported by award T32HL007208 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the US National Institutes of Health.
B.M.P. serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer (Zoll), and he serves on the Steering Committee of the Yale Open-Data Project funded by the Medtronic. P.V. received an unrestricted grant from GlaxoSmithKline to build the CoLaus study. G.T., H.H., A.K., K. Stefansson and U.T. are employees of deCODE Genetics/Amgen, a biotechnology company. I.B. and spouse own stock in GlaxoSmithKline and Incyte, Ltd. S. Kathiresan serves on scientific advisory boards for Merck, Celera, American Genomics and Catabasis. He has received unrestricted research grants from Merck and Pfizer.
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Do, R., Willer, C., Schmidt, E. et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 45, 1345–1352 (2013). https://doi.org/10.1038/ng.2795
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