Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Copyright policy )Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
- Technical University of Munich Germany
- Vrije Universiteit Amsterdam Netherlands
- University of Queensland Australia
- University of Southern Denmark Denmark
- University of Queensland Australia
Netherlands Twin Register (NTR), Adult, Male, HDL, EMC NIHES-01-64-02, Adolescent, European Continental Ancestry Group, Quantitative Trait Loci, 610, Coronary Disease, Polymorphism, Single Nucleotide, Body Mass Index, Cohort Studies, C1, SDG 3 - Good Health and Well-being, 616, 80 and over, Humans, Genetic Predisposition to Disease, Genetic Testing, Polymorphism, EMC MGC-02-96-01, Aged, Genetics & Heredity, Aged, 80 and over, Sex Characteristics, Genome, Genome, Human, Adolescent, Adult, Aged, Aged; 80 and over, Body Mass Index, Cholesterol; HDL; blood, Cohort Studies, Coronary Disease; blood/genetics, European Continental Ancestry Group; genetics, Female, Genetic Predisposition to Disease, Genetic Testing, Genome; Human; genetics, Humans, Lipids; blood, Male, Metabolic Networks and Pathways; genetics, Middle Aged, Phenotype, Polymorphism; Single Nucleotide; genetics, Quantitative Trait Loci; genetics, Sex Characteristics, Cholesterol, HDL, Single Nucleotide, Middle Aged, Lipids, Cholesterol, EMC MM-01-39-02, Phenotype, Female, Metabolic Networks and Pathways, Human, EMC COEUR-09
Netherlands Twin Register (NTR), Adult, Male, HDL, EMC NIHES-01-64-02, Adolescent, European Continental Ancestry Group, Quantitative Trait Loci, 610, Coronary Disease, Polymorphism, Single Nucleotide, Body Mass Index, Cohort Studies, C1, SDG 3 - Good Health and Well-being, 616, 80 and over, Humans, Genetic Predisposition to Disease, Genetic Testing, Polymorphism, EMC MGC-02-96-01, Aged, Genetics & Heredity, Aged, 80 and over, Sex Characteristics, Genome, Genome, Human, Adolescent, Adult, Aged, Aged; 80 and over, Body Mass Index, Cholesterol; HDL; blood, Cohort Studies, Coronary Disease; blood/genetics, European Continental Ancestry Group; genetics, Female, Genetic Predisposition to Disease, Genetic Testing, Genome; Human; genetics, Humans, Lipids; blood, Male, Metabolic Networks and Pathways; genetics, Middle Aged, Phenotype, Polymorphism; Single Nucleotide; genetics, Quantitative Trait Loci; genetics, Sex Characteristics, Cholesterol, HDL, Single Nucleotide, Middle Aged, Lipids, Cholesterol, EMC MM-01-39-02, Phenotype, Female, Metabolic Networks and Pathways, Human, EMC COEUR-09
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