Genetic variation in VKORC1 is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has also been linked to parental dementia. However, it is unclear whether the relationship persists for the diagnosis in patients themselves, whether the association holds only for certain forms of dementia, and if those taking warfarin are at greater risk. Here, we use data from 211,423 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. We find that the T-allele in rs9923231 confers a greater risk for vascular dementia (OR=1.28, p=0.0069), but not for general dementia (OR=1.04, p=0.21) or Alzheimer dementia (OR=1.05, p=0.35), and that the risk of vascular dementia is not affected by warfarin use in carriers of the T-allele. Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia.

中文翻译：

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VKORC1的变化与血管性痴呆有关

VKORC1的遗传变异与血液凝结的差异有关，因此与对华法林药物的敏感性有关。VKORC1的变异也与父母痴呆有关。然而，尚不清楚这种关系是否会持续存在于患者自身的诊断中，这种关联是否仅适用于某些形式的痴呆症，以及服用华法林的患者是否处于更大的风险中。在这里，我们使用来自英国生物银行的211,423名参与者的数据来检查VKORC1，痴呆风险以及与华法林使用之间的相互作用。我们发现rs9923231中的T等位基因赋予血管性痴呆的更大风险（OR = 1.28，p = 0.0069），而不是一般性痴呆（OR = 1.04，p = 0.21）或阿尔茨海默氏痴呆（OR = 1.05，p = 0.35），并且在T等位基因携带者中使用华法林不会影响血管性痴呆的风险。我们的研究首次报道了rs9923231与血管性痴呆之间的关联，但是有必要进行进一步的研究以探索潜在的机制，并明确rs9923231与血管性痴呆特征之间的关系。