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

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 & 8 others Michael G. Marmot, George Davey Smith, Debbie A. Lawlor, Mika Kivimaki, John Whittaker, Aroon D. Hingorani, Ian N. Day, Steve E. Humphries

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    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.

    LanguageEnglish
    Pages456-467
    Number of pages12
    JournalAnnals of Human Genetics
    Volume75
    Issue number4
    DOIs
    Publication statusPublished - 1 Jul 2011

    Keywords

    • Human CVD BeadChip
    • VWF and ABO
    • VWF levels

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Cite this

    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. / Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip. In: Annals of Human Genetics. 2011 ; Vol. 75, No. 4. pp. 456-467.
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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.",
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    author = "Delilah Zabaneh and Gaunt, {Tom R.} and Meena Kumari and Fotios Drenos and Sonia Shah and Diane Berry and Chris Power and Elina Hypponen and Tina Shah and Jutta Palmen and Jacky Pallas and Talmud, {Philippa J.} and Casas, {Juan Pablo} and Reecha Sofat and Gordon Lowe and Ann Rumley and Morris, {Richard W.} and Whincup, {Peter H.} and Santiago Rodriguez and Shah Ebrahim and Marmot, {Michael G.} and Smith, {George Davey} and Lawlor, {Debbie A.} and Mika Kivimaki and John Whittaker and Hingorani, {Aroon D.} and Day, {Ian N.} and Humphries, {Steve E.}",
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    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, vol. 75, no. 4, pp. 456-467. https://doi.org/10.1111/j.1469-1809.2011.00654.x

    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.; Humphries, Steve E.

    In: Annals of Human Genetics, Vol. 75, No. 4, 01.07.2011, p. 456-467.

    Research output: Contribution to journalArticle

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    T1 - Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip

    AU - Zabaneh, Delilah

    AU - Gaunt, Tom R.

    AU - Kumari, Meena

    AU - Drenos, Fotios

    AU - Shah, Sonia

    AU - Berry, Diane

    AU - Power, Chris

    AU - Hypponen, Elina

    AU - Shah, Tina

    AU - Palmen, Jutta

    AU - Pallas, Jacky

    AU - Talmud, Philippa J.

    AU - Casas, Juan Pablo

    AU - Sofat, Reecha

    AU - Lowe, Gordon

    AU - Rumley, Ann

    AU - Morris, Richard W.

    AU - Whincup, Peter H.

    AU - Rodriguez, Santiago

    AU - Ebrahim, Shah

    AU - Marmot, Michael G.

    AU - Smith, George Davey

    AU - Lawlor, Debbie A.

    AU - Kivimaki, Mika

    AU - Whittaker, John

    AU - Hingorani, Aroon D.

    AU - Day, Ian N.

    AU - Humphries, Steve E.

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