Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease. 2022

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

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. To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. 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). 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. 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.

UI MeSH Term Description Entries
D010300 Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D003069 Coffee A beverage made from ground COFFEA beans (SEEDS) infused in hot water. It generally contains CAFFEINE and THEOPHYLLINE unless it is decaffeinated.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000428 Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. Alcohol Consumption,Alcohol Intake,Drinking, Alcohol,Alcohol Drinking Habits,Alcohol Drinking Habit,Alcohol Intakes,Consumption, Alcohol,Drinking Habit, Alcohol,Habit, Alcohol Drinking,Habits, Alcohol Drinking,Intake, Alcohol
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D012907 Smoking Willful or deliberate act of inhaling and exhaling SMOKE from burning substances or agents held by hand. Smoking Behaviors,Smoking Habit,Behavior, Smoking,Behaviors, Smoking,Habit, Smoking,Habits, Smoking,Smoking Behavior,Smoking Habits
D055106 Genome-Wide Association Study An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers to identify gene candidates or quantitative trait loci associated with a specific organism trait or specific disease or condition. Genome Wide Association Analysis,Genome Wide Association Study,GWA Study,Genome Wide Association Scan,Genome Wide Association Studies,Whole Genome Association Analysis,Whole Genome Association Study,Association Studies, Genome-Wide,Association Study, Genome-Wide,GWA Studies,Genome-Wide Association Studies,Studies, GWA,Studies, Genome-Wide Association,Study, GWA,Study, Genome-Wide Association
D057182 Mendelian Randomization Analysis The use of the GENETIC VARIATION of known functions or phenotypes to correlate the causal effects of those functions or phenotypes with a disease outcome. Analysis, Mendelian Randomization

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