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.

Original publication

DOI

10.1038/ng.291

Type

Journal article

Journal

Nat Genet

Publication Date

01/2009

Volume

41

Pages

56 - 65

Keywords

Adult, Alleles, Cholesterol, HDL, Cholesterol, LDL, Dyslipidemias, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Liver, Male, Meta-Analysis as Topic, Middle Aged, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, RNA, Messenger, Reproducibility of Results, Syndrome, Triglycerides