Related Factors with Vascular Dementia: A Two-Sample Mendelian Randomization Study

Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (t⁶A) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, p < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, p = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, p = 0.012). The MR analysis indicated that metabolites (t⁶A) may be causally associated with a positive effect on VD.