| Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip. | |
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MedLine Citation:
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PMID: 21534939 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We have used the gene-centric Illumina HumanCVD BeadChip to identify common genetic determinants of Von Willebrand factor (vWF) levels in healthy men and women. The Whitehall II (WHII) study (n= 5592) and the British Women's Heart and Health Study (BWHHS) (n= 3445) were genotyped using the HumanCVD BeadChip. Replication was conducted in the British Regional Heart Study (n= 3897) and 1958 Birth Cohort (n= 5048). We identified 48 single nucleotide polymorphisms (SNPs) in four genes/regions associated with vWF at P < 10(-4) . These included 19 SNPs at the ABO blood group locus with the lead variant being rs657152 (P= 9.7 × 10(-233) ). The lead variant in the 24 VWF SNPs was rs1063856 (P= 2.3 × 10(-20) ). SNPs at ESR1 (rs6909023) and NRG1(rs1685103) showed modest associations with vWF, but these were not confirmed in a meta-analysis. Using variable selection, five SNPs at the locus for ABO and two for VWF were found to have independent associations with vWF levels. After adjustment for age and gender, the selected ABO SNPs explained 15% and the VWF SNPs an additional 2% of the variance in vWF levels. Individuals at opposite tails of the additive seven SNP allele score exhibited substantial differences in vWF levels. These data demonstrate that multiple common alleles with small effects make, in combination, important contributions to individual differences in vWF levels. |
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Authors:
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Delilah Zabaneh; Tom R Gaunt; Meena Kumari; Fotios Drenos; Sonia Shah; Diane Berry; Chris Power; Elina Hypponen; Tina Shah; Jutta Palmen; Jacky Pallas; Philippa J Talmud; Juan Pablo Casas; Reecha Sofat; Gordon Lowe; Ann Rumley; Richard W Morris; Peter H Whincup; Santiago Rodriguez; Shah Ebrahim; Michael G Marmot; George Davey Smith; Debbie A Lawlor; Mika Kivimaki; John Whittaker; Aroon D Hingorani; Ian N Day; Steve E Humphries |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-28 |
Journal Detail:
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Title: Annals of human genetics Volume: - ISSN: 1469-1809 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-5-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416661 Medline TA: Ann Hum Genet Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London. |
Affiliation:
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University College London Genetics Institute, Department of Genetics, Environment and Evolution, London, UK MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, UK Centre for Cardiovascular Genetics, Department of Medicine, University College London, London, UK Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, UK Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK Centre for Clinical Pharmacology, Department of Medicine, University College London, London, UK Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK UCL Department of Primary Care and Population Health, Royal Free campus, London, UK Division of Community Health Sciences, St George's University of London, London SW17 0RE. |
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