Common variants at 30 loci contribute to polygenic dyslipidemia
Copyright policy )Common variants at 30 loci contribute to polygenic dyslipidemia
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.
- Malmö University Sweden
- Wellcome Trust United Kingdom
- Boston College United States
- University of Helsinki Finland
- National Institutes of Health United States
Adult, Male, Multifactorial Inheritance, Cholesterol, HDL, Quantitative Trait Loci, Reproducibility of Results, Cholesterol, LDL, Middle Aged, Polymorphism, Single Nucleotide, Delta-5 Fatty Acid Desaturase, Phenotype, Gene Expression Regulation, Liver, Meta-Analysis as Topic, Humans, Female, RNA, Messenger, Alleles, Dyslipidemias, Genome-Wide Association Study
Adult, Male, Multifactorial Inheritance, Cholesterol, HDL, Quantitative Trait Loci, Reproducibility of Results, Cholesterol, LDL, Middle Aged, Polymorphism, Single Nucleotide, Delta-5 Fatty Acid Desaturase, Phenotype, Gene Expression Regulation, Liver, Meta-Analysis as Topic, Humans, Female, RNA, Messenger, Alleles, Dyslipidemias, Genome-Wide Association Study
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