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Variation in VKORC1 Is Associated with Vascular Dementia

Authors: Jure Mur; Daniel L. McCartney; Daniel I. Chasman; Peter M. Visscher; Graciela Muniz-Terrera; Simon R. Cox; Tom C. Russ; +1 Authors

Variation in VKORC1 Is Associated with Vascular Dementia

Abstract

Background: The genetic variant rs9923231 ( VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer’s disease in the parents of participants, with suggestive evidence for an association for rs9923231 ( p = 1.8×10 –7 ), which was included in the genome-wide significant KAT8 locus. Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk. Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia ( p < 4.6×10 –6 ). The T-allele in rs9923231 was linked to a lower warfarin dose (β perT - allele = –0.29, p < 2×10 –16 ) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele. Conclusion: 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.

Country
United Kingdom
Keywords

2800 Neuroscience, Male, Genotype, Dementia, Vascular, 3203 Clinical Psychology, Anticoagulants, 2717 Geriatrics and Gerontology, Middle Aged, Vascular dementia, Polymorphism, Single Nucleotide, Vitamin K Epoxide Reductases, 2738 Psychiatry and Mental health, Genetics, Humans, Female, Genetic Predisposition to Disease, Warfarin, Alzheimer disease, Research Article, Aged

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    7
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Top 10%
Average
Top 10%
Green
hybrid