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Variation in VKORC1 is associated with vascular dementia

By Jure Mur, Daniel L. McCartney, Daniel I. Chasman, Peter M Visscher, Graciela Muniz-Terrera, Simon R Cox, Tom C. Russ, Riccardo E. Marioni

Posted 03 Aug 2020
bioRxiv DOI: 10.1101/2020.07.31.231126

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. ### Competing Interest Statement The authors have declared no competing interest.

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