Common variants at 30 loci contribute to polygenic dyslipidemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-01

AUTHORS

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, Josée 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, Gonçalo R Abecasis, Karen L Mohlke, L Adrienne Cupples

ABSTRACT

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. More... »

PAGES

56-65

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.291

DOI

http://dx.doi.org/10.1038/ng.291

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044117587

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19060906


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