@article{2996928,
    title = "Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease",
    author = "Domenighetti, C. and Sugier, P.-E. and Sreelatha, A.A.K. and Schulte, C. and Grover, S. and Mohamed, O. and Portugal, B. and May, P. and Bobbili, D.R. and Radivojkov-Blagojevic, M. and Lichtner, P. and Singleton, A.B. and Hernandez, D.G. and Edsall, C. and Mellick, G.D. and Zimprich, A. and Pirker, W. and Rogaeva, E. and Lang, A.E. and Koks, S. and Taba, P. and Lesage, S. and Brice, A. and Corvol, J.-C. and Chartier-Harlin, M.-C. and Mutez, E. and Brockmann, K. and Deutschländer, A.B. and Hadjigeorgiou, G.M. and Dardiotis, E. and Stefanis, L. and Simitsi, A.M. and Valente, E.M. and Petrucci, S. and Duga, S. and Straniero, L. and Zecchinelli, A. and Pezzoli, G. and Brighina, L. and Ferrarese, C. and Annesi, G. and Quattrone, A. and Gagliardi, M. and Matsuo, H. and Kawamura, Y. and Hattori, N. and Nishioka, K. and Chung, S.J. and Kim, Y.J. and Kolber, P. and Van De Warrenburg, B.P.C. and Bloem, B.R. and Aasly, J. and Toft, M. and Pihlstrøm, L. and Guedes, L.C. and Ferreira, J.J. and Bardien, S. and Carr, J. and Tolosa, E. and Ezquerra, M. and Pastor, P. and Diez-Fairen, M. and Wirdefeldt, K. and Pedersen, N.L. and Ran, C. and Belin, A.C. and Puschmann, A. and Hellberg, C. and Clarke, C.E. and Morrison, K.E. and Tan, M. and Krainc, D. and Burbulla, L.F. and Farrer, M.J. and Krüger, R. and Gasser, T. and Sharma, M. and Elbaz, A.",
    journal = "Journal of Parkinson's Disease",
    year = "2022",
    volume = "12",
    number = "1",
    pages = "267-282",
    publisher = "IOS Press BV",
    issn = "1877-7171, 1877-718x",
    doi = "10.3233/JPD-212851",
    keywords = "aged;  ancestry group;  Article;  case control study;  coffee consumption;  cohort analysis;  controlled study;  disease duration;  drinking behavior;  genetic polymorphism;  genetic variability;  genome-wide association study;  human;  incidence;  lifestyle modification;  major clinical study;  Mendelian randomization analysis;  observational study;  Parkinson disease;  patient participation;  pleiotropy;  prevalence;  sample size;  smoking;  survival rate",
    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. © 2022 - IOS Press. All rights reserved."
}