Abstract

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.

1. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, Michigan 48109, USA.
2. Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy 09042.
3. Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
4. Unitá Operativa Geriatria, Istituto per la Patologia Endocrina e Metabolica, Rome, Italy.
5. Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
6. Clinical Trial Service Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.
7. Centre National de Génotypage, Institut Génomique, Commissariat à l'Énergie Atomique, 2 rue Gaston Crémieux, CP 5721, 91057 Evry Cedex, France.
8. Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK.
9. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
10. U872 Institut National de la Santé et de la Recherche Médicale (INSERM) and Département de Santé Publique et d'Informatique Médicale, Faculté de Médecine René Descartes, 15 rue de l'Ecole de Médecine, 75270 Paris, France.
11. U557 INSERM; U1125 Institut National de la Recherche Agronomique (INRA); Cnam; Paris 13 University; Centre de Recherche en Nutrition Humaine (CRNH) IdF, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France.
12. Laboratory of Analytical Biochemistry, Department of Health and Functional Capacity, National Public Health Institute, 00300 Helsinki, Finland.
13. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
14. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
15. Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel St. London WC1E 7HT, UK.
16. Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, 00300 Helsinki, Finland and Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
17. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
18. These authors contributed equally to the work.

Correspondence to: Gonçalo R Abecasis¹ e-mail: goncalo@umich.edu

Correspondence to: Karen L Mohlke¹⁷ e-mail: mohlke@med.unc.edu

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index