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 Rudan, Åsa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A Hicks, Mario Falchi, Gonneke Willemsen and Jouke-Jan Hottenga (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature Genetics, 41 1: 47-55. doi:10.1038/ng.269


Author 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 Rudan
Åsa 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
Title Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Formatted title
Loci influencing lipid levels and coronary heart disease
risk in 16 European population cohorts
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2009-01
Year available 2008
Sub-type Article (original research)
DOI 10.1038/ng.269
Volume 41
Issue 1
Start page 47
End page 55
Total pages 9
Editor Myles Axton
Place of publication United States
Publisher Nature Publishing Group
Language eng
Subject C1
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.
Formatted 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.

Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 23 Mar 2010, 19:01:27 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital