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

Yurii S. Aulchenko, Samuli Ripatti, Ida Lindqvist, Dorret Boomsma, Iris M. Heid, Peter P. Pramstaller, Brenda W.J.H. Penninx, A. Cecile J.W. Janssens, James F. Wilson, Tim Spector, Nicholas G. Martin, Nancy L. Pedersen, Kirsten Ohm Kyvik, Jaakko Kaprio, Albert Hofman, Nelson B. Freimer, Marjo Riitta Jarvelin, Ulf Gyllensten, Harry Campbell, Igor RudanÅsa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A. Hicks, Mario Falchi, Gonneke Willemsen, Jouke Jan Hottenga, Eco J.C. De Geus, Grant W. Montgomery, John Whitfield, Patrik Magnusson, Juha Saharinen, Markus Perola, Kaisa Silander, Aaron Isaacs, Eric J.G. Sijbrands, Andre G. Uitterlinden, Jacqueline C.M. Witteman, Ben A. Oostra, Paul Elliott, Aimo Ruokonen, Chiara Sabatti, Christian Gieger, Thomas Meitinger, Florian Kronenberg, Angela Döring, H. Erich Wichmann, Johannes H. Smit, Mark I. McCarthy, Cornelia M. Van Duijn, Leena Peltonen

Research output: Contribution to journalArticlepeer-review

731 Scopus citations

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 × 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 × 10-11; LDL, P = 2.6 × 10 -10), TMEM57 (TC, P = 5.4 × 10-10), CTCF-PRMT8 region (HDL, P = 8.3 × 10-16), DNAH11 (LDL, P = 6.1 × 10-9), FADS3-FADS2 (TC, P = 1.5 × 10-10; LDL, P = 4.4 × 10-13) and MADD-FOLH1 region (HDL, P = 6 × 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.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalNature Genetics
Volume41
Issue number1
DOIs
StatePublished - Jan 2009

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