Discovery and refinement of loci associated with lipid levels · SciRah

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Discovery and refinement of loci associated with lipid levels

Cristen J. Willer^{a b c d}✉, Ellen M. Schmidt^b, Sebanti Sengupta^a, J Chen^{a e f g}, Jennifer L. Bragg‐Gresham^{a h i}, Anne Jackson^{a j}, Carlo Sidore^{a h i k l m}, Tanya M. Teslovich^a, Michael Boehnke^{a n}, Abecasis Gb^{a o p}✉, Gina Marie Peloso

Nature Genetics Nature Portfolio2013-10-06 3,021 citations58 references

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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.

TL;DRIt is found 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. (Semantic Scholar)

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^aCenter for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
^bDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA
^cDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
^dDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
^eBroad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA
^fCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
^gDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA
^hDepartment of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
ⁱScience for Life Laboratory, Uppsala University, Uppsala, Sweden
^jWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom
^kDipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy
^lIstituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy
^mDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
ⁿDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA
^oDivision of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA
^pHarvard Medical School, Boston MA 02115, USA
^qDepartment of Medical Genetics, University of Lausanne, Lausanne, Switzerland
^rService of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
^sFramingham Heart Study, Framingham, MA, USA
^tDivision of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
^uMassachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA
^vGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
^wCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
^xDepartment of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
^yDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
^zEstonian Genome Center of the University of Tartu, Tartu, Estonia
^aaInstitute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
^abMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom
^acDivision of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA
^adDivision of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA
^aeCardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland
^afCenter for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
^agDepartment of Genetics, Washington University School of Medicine, USA
^ahWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
^aiDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden
^ajUppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
^akCentre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom
^alDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
^amHjelt Institute, Department of Public Health, University of Helsinki, Finland
^anUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK
^aoCentre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom
^apDepartment of Statistical Sciences, University College of London, London, United Kingdom
^aqCentre for Medical Systems Biology, Leiden, the Netherlands
✉Corresponding author