| Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. | |
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MedLine Citation:
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PMID: 19060911 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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; Asa 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; |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-12-07 |
Journal Detail:
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Title: Nature genetics Volume: 41 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-29 Completed Date: 2009-01-23 Revised Date: 2010-09-02 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 47-55 Citation Subset: IM |
Affiliation:
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[1] Department of Epidemiology and Biostatistics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [2] These authors contributed equally to this work. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Grant Support | |
ID/Acronym/Agency:
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089061//Wellcome Trust; 5R01HL087679-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, HDL; 0/Lipids |
| Investigator | |
Investigator/Affiliation:
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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 / ; Asa 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 / |
| Comments/Corrections | |
Comment In:
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Nat Genet. 2009 Jan;41(1):5-6
[PMID:
19112455
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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