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

Zabaneh, Delilah, Gaunt, Tom R., Kumari, Meena, Drenos, Fotios, Shah, Sonia, Berry, Diane, Power, Chris, Hypponen, Elina, Shah, Tina, Palmen, Jutta, Pallas, Jacky, Talmud, Philippa J., Casas, Juan Pablo, Sofat, Reecha, Lowe, Gordon, Rumley, Ann, Morris, Richard W., Whincup, Peter H., Rodriguez, Santiago, Ebrahim, Shah, Marmot, Michael G., Smith, George Davey, Lawlor, Debbie A., Kivimaki, Mika, Whittaker, John, Hingorani, Aroon D., Day, Ian N. and Humphries, Steve E. (2011) Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip. Annals of Human Genetics, 75 4: 456-467. doi:10.1111/j.1469-1809.2011.00654.x


Author Zabaneh, Delilah
Gaunt, Tom R.
Kumari, Meena
Drenos, Fotios
Shah, Sonia
Berry, Diane
Power, Chris
Hypponen, Elina
Shah, Tina
Palmen, Jutta
Pallas, Jacky
Talmud, Philippa J.
Casas, Juan Pablo
Sofat, Reecha
Lowe, Gordon
Rumley, Ann
Morris, Richard W.
Whincup, Peter H.
Rodriguez, Santiago
Ebrahim, Shah
Marmot, Michael G.
Smith, George Davey
Lawlor, Debbie A.
Kivimaki, Mika
Whittaker, John
Hingorani, Aroon D.
Day, Ian N.
Humphries, Steve E.
Title Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip
Journal name Annals of Human Genetics   Check publisher's open access policy
ISSN 0003-4800
1469-1809
Publication date 2011-01-01
Sub-type Article (original research)
DOI 10.1111/j.1469-1809.2011.00654.x
Volume 75
Issue 4
Start page 456
End page 467
Total pages 12
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell
Language eng
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. © 2011 The Authors Annals of Human Genetics
Keyword Human CVD BeadChip
VWF and ABO
VWF levels
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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