Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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We especially thank the more than 196,000 volunteers who participated in our study. Detailed acknowledgment of funding sources is provided in the Supplementary Note.
B.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.
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Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat Genet 45, 1274–1283 (2013). https://doi.org/10.1038/ng.2797
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