Discovery and refinement of loci associated with lipid levels

Abstract

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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Affiliated Institutions

• Science for Life Laboratory SE
• Institute of Genetics and Cancer GB
• Harokopio University of Athens GR
• Harvard University US
• University of Dundee GB
• Universität Ulm DE
• University Hospital Heidelberg DE
• University of California, Los Angeles US
• Johns Hopkins Medicine US
• Ninewells Hospital GB
• Umeå University SE
• University of Milano-Bicocca IT
• King's College London GB
• University College London GB
• Helmholtz Zentrum München DE
• Amsterdam UMC Location University of Amsterdam NL
• University of Groningen NL
• University of Pennsylvania US
• University of Oklahoma Health Sciences Center US
• MedStar Health US
• Broad Institute US
• University of North Carolina at Chapel Hill US
• Cedars-Sinai Medical Center US
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• Addenbrooke's Hospital GB
• MRC Unit for Lifelong Health and Ageing GB
• University of Edinburgh GB
• National Human Genome Research Institute US
• NIHR Cambridge Biomedical Research Centre
• Massachusetts General Hospital US
• deCODE Genetics (Iceland) IS
• Tri-Service General Hospital TW
• Oulu University Hospital FI
• Centre for Human Genetics GB
• Institute for Molecular Medicine Finland FI
• University of Oulu FI
• Finnish Institute for Health and Welfare FI
• Imperial College London GB
• Uppsala University SE
• University of Helsinki FI
• Centre for Medical Systems Biology NL
• Ealing Hospital GB
• Fimlab (Finland) FI
• Brigham and Women's Hospital US
• Boston Children's Hospital US
• Uganda Virus Research Institute UG
• University of Cambridge GB
• The University of Texas Health Science Center at Houston US
• National Institute on Aging US
• Boston University US
• University of Oxford GB
• Lund University SE
• Eurac Research IT
• University Medical Center Groningen NL
• National Defense Medical Center TW
• Erasmus MC NL
• Institute of Genetic and Biomedical Research IT
• Tampere University FI
• Western General Hospital GB
• University of Maryland, Baltimore US
• Scania (Sweden) SE
• University of Mannheim DE
• University of Sassari IT
• Karolinska University Hospital SE
• National Health Research Institutes TW
• William Harvey Research Institute GB
• Oxford Centre for Diabetes, Endocrinology and Metabolism GB
• Queen Mary University of London GB
• HudsonAlpha Institute for Biotechnology US
• University of Michigan US
• University Hospital of Geneva CH
• University of Lübeck DE
• MRC Epidemiology Unit GB
• Wellcome Sanger Institute GB
• Johns Hopkins University US
• University of Tartu EE
• Translational Therapeutics (United States) US
• Heidelberg University DE
• Medizinische Hochschule Hannover DE
• University of Lausanne CH

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