Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-01-13

AUTHORS

Sekar Kathiresan, Olle Melander, Candace Guiducci, Aarti Surti, Noël P Burtt, Mark J Rieder, Gregory M Cooper, Charlotta Roos, Benjamin F Voight, Aki S Havulinna, Björn Wahlstrand, Thomas Hedner, Dolores Corella, E Shyong Tai, Jose M Ordovas, Göran Berglund, Erkki Vartiainen, Pekka Jousilahti, Bo Hedblad, Marja-Riitta Taskinen, Christopher Newton-Cheh, Veikko Salomaa, Leena Peltonen, Leif Groop, David M Altshuler, Marju Orho-Melander

ABSTRACT

Blood concentrations of lipoproteins and lipids are heritable1 risk factors for cardiovascular disease2,3. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue4) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 × 10−8 for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease5. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care. More... »

PAGES

189-197

Journal

TITLE

Nature Genetics

ISSUE

2

VOLUME

40

Author Affiliations

  • Department of Medicine, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, 20502, Malmö, Sweden
  • Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Department of Genome Sciences, University of Washington, 98195, Seattle, Washington, USA
  • Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, 20502, Malmö, Sweden
  • Department of Molecular Biology, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • National Public Health Institute, 00300, Helsinki, Finland
  • Department of Clinical Pharmacology, Sahlgrenska University Hospital, 41345, Göteborg, Sweden
  • Department of Preventive Medicine, School of Medicine, University of Valencia and CIBER Fisiopatología de la Obesidad y Nutrition, 46010, Valencia, Spain
  • Department of Endocrinology, Singapore General Hospital, 169608, Singapore
  • Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Nutrition and Genomics Laboratory, 02111, Boston, Massachusetts, USA
  • Department of Internal Medicine, University Hospital Malmö, Lund University, 20502, Malmö, Sweden
  • Department of Epidemiological Research, University Hospital Malmö, Lund University, 20502, Malmö, Sweden
  • Department of Medicine, University of Helsinki, 00029, Helsinki, Finland
  • Wellcome Trust Sanger Institute, CB10 1SA, Cambridge, UK
  • Department of Medicine, Helsinki University Hospital, 00029, Helsinki, Finland
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.75

    DOI

    http://dx.doi.org/10.1038/ng.75

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013290784

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18193044


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