Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip.


Zabaneh, D; Gaunt, TR; Kumari, M; Drenos, F; Shah, S; Berry, D; Power, C; Hypponen, E; Shah, T; Palmen, J; Pallas, J; Talmud, PJ; Casas, JP; Sofat, R; Lowe, G; Rumley, A; Morris, RW; Whincup, PH; Rodriguez, S; Ebrahim, S; Marmot, MG; Smith, GD; Lawlor, DA; Kivimaki, M; Whittaker, J; Hingorani, AD; Day, IN; Humphries, SE; (2011) Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip. Annals of human genetics. ISSN 0003-4800 DOI: https://doi.org/10.1111/j.1469-1809.2011.00654.x

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Abstract

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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 21534939
Web of Science ID: 292360800002
URI: http://researchonline.lshtm.ac.uk/id/eprint/872

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