Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson’s Disease

Abstract

Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

Plasma Caffeine Levels and Risk of Alzheimer’s Disease and Parkinson’s Disease: Mendelian Randomization Study

“…This also makes physiological sense, as those individuals who metabolize caffeine more slowly will tend to drink less coffee to achieve the same levels of plasma caffeine. A previous MR study found no association between genetically predicted coffee consumption and Parkinson's disease [20], which is in line with our overall null results for genetically predicted plasma caffeine levels and this disease.…”

Identifying Protective Drugs for Parkinson's Disease in Health‐Care Databases Using Machine Learning

“…The fact that drugs used in nicotine dependence were inversely associated with PD in our study, even though these drugs are not used frequently, is a strong argument in favor of the validity of our PD case ascertainment method and ML‐based signal detection approach. The inverse association between smoking and PD is indeed one of the most consistent observations in PD epidemiology, 42 and recent Mendelian randomization studies support a causal association 43 . Because drugs for nicotine dependence were retained in the models, our analyses are indirectly and partially adjusted for smoking.…”

The Interaction betweenHLA‐DRB1and Smoking in Parkinson's Disease Revisited

“…Recent MR studies showed an inverse association between genetically predicted smoking and PD 15‐18 . These findings are in favor of a causal role of smoking in PD, but the underlying mechanisms remain unknown and gene–environment interactions analyses may contribute to their understanding.…”

“…Recent MR studies showed an inverse association between genetically predicted smoking and PD. [15][16][17][18] These findings are in favor of a causal role of smoking in PD, but the underlying mechanisms remain unknown and gene-environment interactions analyses may contribute to their understanding. The interaction pattern we found is similar to the interaction between selfreported smoking and rs660895 reported by Chuang et al 7 Our study represents a fully independent replication using a different approach to define smoking (MR) and SNP-based imputation of HLA amino acids that allowed us to examine this interaction at the AA level.…”