Document Detail


Genetic variants associated with Von Willebrand factor levels in healthy men and women identified using the HumanCVD BeadChip.
MedLine Citation:
PMID:  21534939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2011-04-28
Journal Detail:
Title:  Annals of human genetics     Volume:  75     ISSN:  1469-1809     ISO Abbreviation:  Ann. Hum. Genet.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-14     Completed Date:  2011-09-30     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0416661     Medline TA:  Ann Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  456-67     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.
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MeSH Terms
Descriptor/Qualifier:
ABO Blood-Group System / genetics
Female
Genetic Techniques
Genotype
Humans
Male
Meta-Analysis as Topic
Middle Aged
Polymorphism, Single Nucleotide*
Population Surveillance
von Willebrand Factor / genetics*
Grant Support
ID/Acronym/Agency:
068545/Z/02//Wellcome Trust; AG13196/AG/NIA NIH HHS; FS05/125//British Heart Foundation; G0000934//Department of Health; G0000934//Medical Research Council; G0600705//Medical Research Council; G0601354//Medical Research Council; G0601653//Department of Health; G0601653//Medical Research Council; G0902037//Medical Research Council; G19/35//Medical Research Council; HL36310/HL/NHLBI NIH HHS; PG/07/131/24254//British Heart Foundation; PG/07/133/24260//British Heart Foundation; PG97012//British Heart Foundation; RG/08/008//British Heart Foundation; RG/08/008/25291//British Heart Foundation; RG/08/013/25942//British Heart Foundation; RG/10/12/28456//British Heart Foundation; SP/07/007/23671//British Heart Foundation; U01 DK062418/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/ABO Blood-Group System; 0/von Willebrand Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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