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.

The Australian Parkinson’s Genetics Study (APGS) - pilot (N = 1,532)

“…This should be interpreted with caution, given the small sample size. Also, a recent Mendelian randomisation study by us [75] indicated that the continuation of the smoking habit rather than smoking heaviness (i.e., numbers of cigarettes smoked per day) is what may exert the protective effect of smoking over PD risk.…”

“…In particular, age, mood disorders, consumption of well water [9], head injury [10], and exposure to environmental toxins [11,12] have been consistently associated with an increased PD risk. On the contrary, smoking and caffeine have been inversely related to PD risk and positively correlated with a later age of onset [13,14], suggesting a putative protective effect that needs further exploration. Associations with alcohol remain controversial [15].…”

Australian Parkinson’s Genetics Study (APGS): pilot (n=1532)

“… 6–8 In particular, age, mood disorders, consumption of well water, 9 head injury 10 and exposure to environmental toxins 11 12 have been consistently associated with an increased PD risk. On the contrary, smoking and caffeine consumption have been inversely related to PD risk and positively correlated with a later age of onset, 13 14 suggesting a putative protective effect that needs further exploration. Associations with alcohol drinking remain controversial.…”