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Olle Melander

Principal investigator

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Common variants at 30 loci contribute to polygenic dyslipidemia

Author

  • Sekar Kathiresan
  • Cristen J. Willer
  • Gina M. Peloso
  • Serkalem Demissie
  • Kiran Musunuru
  • Eric E. Schadt
  • Lee Kaplan
  • Derrick Bennett
  • Yun Li
  • Toshiko Tanaka
  • Benjamin F. Voight
  • Lori L. Bonnycastle
  • Anne U. Jackson
  • Gabriel Crawford
  • Aarti Surti
  • Candace Guiducci
  • Noel P. Burtt
  • Sarah Parish
  • Robert Clarke
  • Diana Zelenika
  • Kari A. Kubalanza
  • Mario A. Morken
  • Laura J. Scott
  • Heather M. Stringham
  • Pilar Galan
  • Amy J. Swift
  • Johanna Kuusisto
  • Richard N. Bergman
  • Jouko Sundvall
  • Markku Laakso
  • Luigi Ferrucci
  • Paul Scheet
  • Serena Sanna
  • Manuela Uda
  • Qiong Yang
  • Kathryn L. Lunetta
  • Josee Dupuis
  • Paul I. W. de Bakker
  • Christopher J. O'Donnell
  • John C. Chambers
  • Jaspal S. Kooner
  • Serge Hercberg
  • Pierre Meneton
  • Edward G. Lakatta
  • Angelo Scuteri
  • David Schlessinger
  • Jaakko Tuomilehto
  • Francis S. Collins
  • Leif Groop
  • David Altshuler
  • Rory Collins
  • G. Mark Lathrop
  • Olle Melander
  • Veikko Salomaa
  • Leena Peltonen
  • Marju Orho-Melander
  • Jose M. Ordovas
  • Michael Boehnke
  • Goncalo R. Abecasis
  • Karen L. Mohlke
  • L. Adrienne Cupples

Summary, in English

Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension

Publishing year

2009

Language

English

Pages

56-65

Publication/Series

Nature Genetics

Volume

41

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718