Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

TitleLoci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
Publication TypeJournal Article
Year of Publication2009
AuthorsAulchenko, YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, Penninx BWJH, Janssens CAJW, Wilson JF, Spector T, Martin NG, Pedersen NL, Kyvik KO, Kaprio J, Hofman A, Freimer NB, Jarvelin M-R, Gyllensten U, Campbell H, Rudan I, Johansson A, Marroni F, Hayward C, Vitart V, Jonasson I, Pattaro C, Wright A, Hastie N, Pichler I, Hicks AA, Falchi M, Willemsen G, Hottenga J-J, de Geus EJC, Montgomery GW, Whitfield J, Magnusson P, Saharinen J, Perola M, Silander K, Isaacs A, Sijbrands EJG, Uitterlinden AG, Witteman JCM, Oostra BA, Elliott P, Ruokonen A, Sabatti C, Gieger C, Meitinger T, Kronenberg F, Döring A, Wichmann H-E, Smit JH, McCarthy MI, van Duijn CM, Peltonen L
Corporate AuthorsENGAGE Consortium
JournalNature genetics
Volume41
Issue1
Pagination47-55
Date Published2009 Jan
ISSN1546-1718
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Body Mass Index, Cholesterol, HDL, Cohort Studies, Coronary Disease, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Testing, Genome, Human, Humans, Lipids, Male, Metabolic Networks and Pathways, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics
Abstract

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.

DOI10.1042/AN20110027
Alternate JournalNat. Genet.