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

Cloé Domenighetti, Pierre Emmanuel Sugier, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Oceáne Mohamed, Berta Portugal, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev KoksPille Taba, Suzanne Lesage, Alexis Brice, Jean Christophe Corvol, Marie Christine Chartier-Harlin, Eugénie Mutez, Kathrin Brockmann, Angela B. Deutschländer, Georges M. Hadjigeorgiou, Efthimos Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Stefano Duga, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Yusuke Kawamura, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P.C. Van De Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrøm, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Monica Diez-Fairen, Karin Wirdefeldt, Nancy L. Pedersen, Caroline Ran, Andrea C. Belin, Andreas Puschmann, Clara Hellberg, Carl E. Clarke, Karen E. Morrison, Manuela Tan, Dimitri Krainc, Lena F. Burbulla, Matt J. Farrer, Rejko Krüger, Thomas Gasser, Manu Sharma, Alexis Elbaz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)267-282
Number of pages16
JournalJournal of Parkinson's disease
Volume12
Issue number1
DOIs
StatePublished - 2022

Keywords

  • Mendelian randomisation
  • Parkinson's disease
  • Smoking
  • alcohol
  • coffee

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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