Year: 2021
Type: article
Study design: Observational Study
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 (βperT - 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.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-201256
Authors: Jure Mur, Daniel L. McCartney, Daniel I. Chasman, Peter M. Visscher, Graciela Muniz-Terrera, Simon R. Cox, Tom C. Russ, Riccardo E. Marioni
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1474360503, G1757703766, Translational Neuroscience - training the next generation of basic neuroscientists to embrace clinical research., G2035013072, G2113082864, G2277832307, Causes and consequence of human trait variation, G3229869697, G3313560989, G3868569194, Complex trait genomics, Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: IV, G5026251150, G5850737185, G6868616705, Evaluating Longitudinal Changes in the Human Structural Connectome in Relation to Cognitive Aging, G7877448516, Women's Health Study: Infrastructure support for cohort follow-up, G829891318, G9000063527
OpenAlex ID: W3134230064