Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease
J Parkinsons Dis. 2022;12(1):267-282.
| Authors/Editors: |
Domenighetti C Sugier PE Sreelatha AAK Schulte C Grover S Mohamed O Portugal B May P Bobbili DR Radivojkov-Blagojevic M Lichtner P Singleton AB Hernandez DG Edsall C Mellick GD Zimprich A Pirker W Rogaeva E Lang AE Koks S Taba P Lesage S Brice A Corvol JC Chartier-Harlin MC Mutez E Brockmann K Deutschländer AB Hadjigeorgiou GM Dardiotis E Stefanis L Simitsi AM Valente EM Petrucci S Duga S Straniero L Zecchinelli A Pezzoli G Brighina L Ferrarese C Annesi G Quattrone A Gagliardi M Matsuo H Kawamura Y Hattori N Nishioka K Chung SJ Kim YJ Kolber P van de Warrenburg BP Bloem BR Aasly J Toft M Pihlstrøm L Guedes LC Ferreira JJ Bardien S Carr J Tolosa E Ezquerra M Pastor P Diez-Fairen M Wirdefeldt K Pedersen NL Ran C Belin AC Puschmann A Hellberg C Clarke CE Morrison KE Tan M Krainc D Burbulla LF Farrer MJ Krüger R Gasser T Sharma M Elbaz A Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium |
|---|---|
| Publication Date: | 2022 |
| Type of Publication: | Journal Article |
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.
