Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: A mendelian randomization study

Abstract Background Observational studies suggest that Parkinson's disease (PD) is associated with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization (MR) to evaluate the effects of PD on the risk of ischemic stroke (IS), IS subtypes, coronary artery disease (CAD) and myocardial infarction (MI). Methods Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Applying a 2-sample MR, we examined associations with IS (34,217 cases and 404,630 controls), IS subtypes (cardioembolic, large artery, small vessel stroke), CAD (60,801 cases and 123,504 controls) and MI (43,676 cases and 128,199 controls) in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed using the random-effects inverse variance weighted approach. Results In European population, genetic predisposition to PD was associated with higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01–1.05; P = 0.002) and CES (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04–1.12; P = 1.29 × 10−4), but not with LAS, SVS, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD. Conclusions This study found that genetic predisposition to PD is associated with higher risk of IS and CES in European population.