Common variants at 30 loci contribute to polygenic dyslipidemia
Författare
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.
Publiceringsår
2009
Språk
Engelska
Sidor
56-65
Publikation/Tidskrift/Serie
Nature Genetics
Volym
41
Issue
1
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Endocrinology and Diabetes
- Cardiac and Cardiovascular Systems
Status
Published
Forskningsgrupp
- Translational Muscle Research
- Cardiovascular Research - Hypertension
ISBN/ISSN/Övrigt
- ISSN: 1546-1718