The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Common variants at 30 loci contribute to polygenic dyslipidemia

På svenska

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
Show all

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.

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

  • Translational Muscle Research
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718