Genetic evidence for protective effects of smoking and drinking behavior on Parkinson’s disease: A Mendelian Randomization study

ABSTRACT Background Observational studies have identified correlations between environmental and lifestyle factors and Parkinson’s disease (PD). However, the causal direction of many of these relationships remains unclear. Objective To infer causal relationships between smoking and alcohol intake and PD. Methods We use a two-sample Mendelian randomization (MR) experimental design to infer causal relationships between smoking ( initiation, age of initiation, heaviness , and cessation ) and alcohol ( drinks per week ) consumption as exposure variables and PD as the health outcome. We also conduct sensitivity analyses, including testing for pleiotropic effects MR-Egger and MR-PRESSO, and multivariable MR to jointly model the effects of drinking and smoking behavior on PD risk. Results Both alcohol intake (OR = 0.69; 95% CI 0.56-0.86; p=0.001). and smoking cessation (comparing current vs. former smokers ) (IVW OR = 0.39; 95% CI 0.22 to 0.69; p=0.001) were causally associated with a reduced risk of PD. In addition, our multivariable MR results provide additional assurance that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior. Conclusion Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers . Increased alcohol intake also had a protective effect over PD risk, and the alcohol dehydrogenase 1B ( ADH1B ) locus is a candidate for further investigating the mechanisms underlying this association.