Letter abstract


Nature Genetics 40, 189 - 197 (2008)
Published online: 13 January 2008 | Corrected online: 29 October 2008 | doi:10.1038/ng.75



There is a Corrigendum (November 2008) associated with this Letter.

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

Sekar Kathiresan1,2,3, Olle Melander4, Candace Guiducci2, Aarti Surti2, Noël P Burtt2, Mark J Rieder5, Gregory M Cooper5, Charlotta Roos6, Benjamin F Voight2,7,8, Aki S Havulinna9, Björn Wahlstrand10, Thomas Hedner10, Dolores Corella11, E Shyong Tai12, Jose M Ordovas13, Göran Berglund14, Erkki Vartiainen9, Pekka Jousilahti9, Bo Hedblad15, Marja-Riitta Taskinen16, Christopher Newton-Cheh1,2,3, Veikko Salomaa9, Leena Peltonen2,9,17,18, Leif Groop6,19, David M Altshuler2,3,7,8,20 & Marju Orho-Melander6

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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 times 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.

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  1. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  2. Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  3. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
  4. Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
  5. Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  6. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
  7. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  8. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  9. National Public Health Institute Helsinki 00300, Finland.
  10. Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg 41345, Sweden.
  11. Department of Preventive Medicine, School of Medicine, University of Valencia and CIBER Fisiopatología de la Obesidad y Nutrition, Valencia 46010, Spain.
  12. Department of Endocrinology, Singapore General Hospital, 169608 Singapore.
  13. Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
  14. Department of Internal Medicine, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
  15. Department of Epidemiological Research, University Hospital Malmö, Lund University, Malmö 20502, Sweden.
  16. Department of Medicine, University of Helsinki, Helsinki 00029, Finland.
  17. Department of Medical Genetics, University of Helsinki, Helsinki 00029, Finland.
  18. Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  19. Department of Medicine, Helsinki University Hospital, Helsinki 00029, Finland.
  20. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Correspondence to: Sekar Kathiresan1,2,3 e-mail: skathiresan@partners.org

Correspondence to: Marju Orho-Melander6 e-mail: marju.orho-melander@med.lu.se

* NOTE: In the version of this article initially published, the institutional affiliation for Dolores Corella was not complete. Her affiliation is with the Department of Preventive Medicine, School of Medicine, University of Valencia and CIBER Fisiopatología de la Obesidad y Nutrition, ISCIII, Valencia, 46010, Spain. The error has been corrected in the HTML and PDF versions of the article.

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