학술논문
Common variants at 30 loci contribute to polygenic dyslipidemia
Document Type
Clinical report
Author
Kathiresan, Sekar; Willer, Cristen J.; Peloso, Gina M.; Demissie, Serkalem; Musunuru, Kiran; Schadt, Eric E.; Kaplan, Lee; Bennett, Derrick; Li, Yun; Tanaka, Toshiko; Voight, Benjamin F.; Bonnycastle, Lori L.; Jackson, Anne U.; Crawford, Gabriel; Surti, Aarti; Guiducci, Candace; Burtt, Noel P.; Parish, Sarah; Clarke, Robert; Zelenika, Diana; Kubalanza, Kari A.; Morken, Mario A.; Scott, Laura J.; Stringham, Heather M.; Galan, Pilar; Swift, Amy J.; Kuusisto, Johanna; Bergman, Richard N.; Sundvall, Jouko; Laakso, Markku; Ferrucci, Luigi; Scheet, Paul; Sanna, Serena; Uda, Manuela; Yang, Qiong; Lunetta, Kathryn L.; Dupuis, Josee; de Bakker, Paul I.W.; O'Donnell, Christopher J.; Chambers, John C.; Kooner, Jaspal S.; Hercberg, Serge; Meneton, Pierre; Lakatta, Edward G.; Scuteri, Angelo; Sclessinger, David; Tuomilehto, Jaakko; Collins, Francis S.; Groop, Leif; Altshuler, David; Collins, Rory; Lathrop, G. Mark; Melander, Olle; Salomaa, Veikko; Peltonen, Leena; Orho-Melander, Marju; Ordovas, Jose M.; Boehnke, Michael; Abecasis, Goncalo R.; Mohlke, Karen L.; Cupples, L. Adrienne
Source
Nature Genetics. January, 2009, Vol. 41 Issue 1, p56, 10 p.
Subject
Language
English
ISSN
1061-4036
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.sup.-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 AMACIL2, 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.sup.-15] for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
Recent genome-wide association studies (GWASs) have localized common DNA sequence variants that contribute to many human phenotypes (1). The success of this approach has been particularly notable for blood lipoprotein [...]
Recent genome-wide association studies (GWASs) have localized common DNA sequence variants that contribute to many human phenotypes (1). The success of this approach has been particularly notable for blood lipoprotein [...]