1. Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson’s Disease
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Athina Simitsi, Grazia Annesi, Hirotaka Matsuo, Leonor Correia Guedes, Mario Ezquerra, Kenya Nishioka, Ashwin Ashok Kumar Sreelatha, Simona Petrucci, Dimitri Krainc, Angela Deutschländer, Ekaterina Rogaeva, Lasse Pihlstrøm, Manu Sharma, Thomas Gasser, Mathias Toft, Jan O. Aasly, Cloé Domenighetti, Monica Diez-Fairen, Milena Radivojkov-Blagojevic, Sandeep Grover, Andrew B. Singleton, Bart P.C. van de Warrenburg, Yun Joong Kim, Andrea Quattrone, Sun Ju Chung, Gianni Pezzoli, Pierre-Emmanuel Sugier, Sulev Kõks, Lena F. Burbulla, Jonathan Carr, Walter Pirker, Efthimos Dardiotis, Karin Wirdefeldt, George D. Mellick, Jean-Christophe Corvol, Dheeraj Reddy Bobbili, Anthony E. Lang, Eugénie Mutez, Georges M. Hadjigeorgiou, Anna Zecchinelli, Laura Brighina, Connor Edsall, Océane Mohamed, Berta Portugal, Andreas Puschmann, Nancy L. Pedersen, Alexander Zimprich, Patrick May, Matthew J. Farrer, Leonidas Stefanis, Yusuke Kawamura, Eduardo Tolosa, Claudia Schulte, Alexis Brice, Caroline Ran, Manuela Tan, Pille Taba, Peter Lichtner, Alexis Elbaz, Dena G. Hernandez, Monica Gagliardi, Andrea Carmine Belin, Joaquim J. Ferreira, Suzanne Lesage, Pierre Kolber, Kathrin Brockmann, Marie-Christine Chartier-Harlin, Carl E Clarke, Karen E. Morrison, Nobutaka Hattori, Stefano Duga, Letizia Straniero, Rejko Krüger, Carlo Ferrarese, Pau Pastor, Soraya Bardien, Clara Hellberg, Bastiaan R. Bloem, Enza Maria Valente, Domenighetti, C, Sugier, P, Sreelatha, A, Schulte, C, Grover, S, Mohamed, O, Portugal, B, May, P, Bobbili, D, Radivojkov-Blagojevic, M, Lichtner, P, Singleton, A, Hernandez, D, Edsall, C, Mellick, G, Zimprich, A, Pirker, W, Rogaeva, E, Lang, A, Koks, S, Taba, P, Lesage, S, Brice, A, Corvol, J, Chartier-Harlin, M, Mutez, E, Brockmann, K, Deutschlander, A, Hadjigeorgiou, G, Dardiotis, E, Stefanis, L, Simitsi, A, Valente, E, 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, S, Kim, Y, Kolber, P, Van De Warrenburg, B, Bloem, B, Aasly, J, Toft, M, Pihlstrom, L, Guedes, L, Ferreira, J, Bardien, S, Carr, J, Tolosa, E, Ezquerra, M, Pastor, P, Diez-Fairen, M, Wirdefeldt, K, Pedersen, N, Ran, C, Belin, A, Puschmann, A, Hellberg, C, Clarke, C, Morrison, K, Tan, M, Krainc, D, Burbulla, L, Farrer, M, Kruger, R, Gasser, T, Sharma, M, and Elbaz, A
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Inverse Association ,Parkinson's disease ,parkinson’s disease ,Alcohol Drinking ,coffee ,Alcohol ,Disease ,epidemiology [Alcohol Drinking] ,Coffee ,Article ,Cellular and Molecular Neuroscience ,symbols.namesake ,chemistry.chemical_compound ,genetics [Parkinson Disease] ,Risk Factors ,epidemiology [Smoking] ,Humans ,Medicine ,ddc:610 ,Coffee drinking ,Aged ,alcohol ,business.industry ,Smoking ,Confounding ,Parkinson Disease ,Odds ratio ,Mendelian Randomization Analysis ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,medicine.disease ,mendelian randomisation ,chemistry ,genetics [Alcohol Drinking] ,Parkinson’s disease ,smoking ,aged ,alcohol drinking ,genome-wide association study ,humans ,mendelian randomization analysis ,risk factors ,parkinson disease ,Mendelian inheritance ,symbols ,etiology [Parkinson Disease] ,Neurology (clinical) ,business ,Genome-Wide Association Study ,Demography - Abstract
Contains fulltext : 248871.pdf (Publisher’s version ) (Open Access) 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.
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- 2022