Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip
Genetic Variants Associated with von Willebrand Factor Levels in Healthy Men and Women Identified Using the HumanCVD BeadChip
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DOI：
10.1111/j.1469-1809.2011.00654.x
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发表时间：
2011-07-01
影响因子：
1.9
通讯作者：
Humphries, Steve E.
中科院分区：
文献类型：
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作者：
Zabaneh, Delilah;Gaunt, Tom R.;Humphries, Steve E.
我们使用以基因为中心的 Illumina HumanCVD BeadChip 来识别健康男性和女性中血管性血友病因子 (vWF) 水平的常见遗传决定因素。Whitehall II (WHII) 研究 (n = 5592) 和英国女性心脏与健康研究 (BWHHS) (n = 3445) 使用 HumanCVD BeadChip 进行基因分型。在英国区域心脏研究 (n = 3897) 和 1958 年出生队列 (n = 5048) 中进行了复制。我们在与 vWF 相关的四个基因/区域中确定了 48 个单核苷酸多态性 (SNP)，P < 10(-4)。其中包括 ABO 血型基因座上的 19 个 SNP，其中主要变异为 rs657152 (P = 9.7 x 10(-233))。 24 个 VWF SNP 中的先导变异是 rs1063856 (P = 2.3 x 10(-20))。 ESR1 (rs6909023) 和 NRG1 (rst1685103) 的 SNP 显示出与 vWF 的适度关联，但这些并未在荟萃分析中得到证实。通过变量选择，发现 ABO 基因座上的 5 个 SNP 和 VWF 基因座上的 2 个 SNP 与 vWF 水平具有独立关联。调整年龄和性别后，选定的 ABO SNP 解释了 vWF 水平差异的 15%，VWF SNP 解释了额外的 2%。位于加性七个 SNP 等位基因评分相对尾部的个体在 vWF 水平上表现出显着差异。这些数据表明，影响较小的多个常见等位基因结合起来，对 vWF 水平的个体差异产生了重要贡献。
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 x 10(-233)). The lead variant in the 24 VWF SNPs was rs1063856 (P = 2.3 x 10(-20)). SNPs at ESR1 (rs6909023) and NRG1(rst1685103) 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.