Abstract
OBJECTIVE: To examine causal associations between risky behavior phenotypes and Parkinson disease using a mendelian randomization approach. METHODS: We used 2-sample mendelian randomization to generate unconfounded estimates using summary statistics from 2 independent, large meta-analyses of genome-wide association studies on risk-taking behaviors (n = 370,771-939,908) and Parkinson disease (cases n = 9,581, controls n = 33,245). We used the inverse variance weighted method as the main method for judging causality. RESULTS: Our results support a strong protective association between the tendency to smoke and Parkinson disease (odds ratio [OR] 0.714 per log odds of ever smoking, 95% confidence interval [CI] 0.568-0.897, p = 0.0041, Cochran Q test p = 0.238; I (2) index 6.3%). Furthermore, we observed risk association trends between automobile speed propensity and the number of sexual partners and Parkinson disease after removal of overlapping loci with other risky traits (OR 1.986 for each 1-SD increase in normalized automobile speed propensity, 95% CI 1.215-3.243, p = 0.0066; OR 1.635 for each 1-SD increase in number of sexual partners, 95% CI 1.165-2.293, p = 0.0049). CONCLUSION: These findings provide support for a causal relationship between general risk tolerance and Parkinson disease and may provide new insights into the pathogenic mechanisms leading to the development of Parkinson disease.