Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease.
Journal: Journal of Parkinson's disease
Volume: 12
Issue: 1
Year of Publication: 2022
Affiliated Institutions:
Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Team "Exposome, heredity, cancer and health", CESP, Villejuif, France.
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany.
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Germany.
Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD, USA.
Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland, Australia.
Department of Neurology, Medical University of Vienna, Austria.
Department of Neurology, Wilhelminenspital, Austria.
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
Department of Neurology and Neurosurgery, University of Tartu, Estonia.
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Department of Neurologie, Paris, France.
Univ. Lille, Inserm, CHU Lille, UMR-S - LilNCog- Centre de Recherche Lille Neurosciences & Cognition, Lille, France.
Department of Neurology, Ludwig Maximilians University of Munich, Germany.
Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
Department of Biomedical Sciences - Humanitas University, Milan, Italy.
Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milano, Italy.
Department of Neurology, San Gerardo Hospital, Monza, Italy.
Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
Institute of Neurology, Magna Graecia University, Catanzaro, Italy.
Institute of Molecular Bioimaging and Physiology National Research Council, Catanzaro, Italy.
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands.
Department of Neurology, St Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
Parkinson's disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia.
Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Terrassa, Barcelona, Spain.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden.
University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, UK.
Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, UK.
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Abstract summary
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.
Authors & Co-authors:
Domenighetti Cloé C
Sugier Pierre-Emmanuel PE
Sreelatha Ashwin Ashok Kumar AAK
Schulte Claudia C
Grover Sandeep S
Mohamed Océane O
Portugal Berta B
May Patrick P
Bobbili Dheeraj R DR
Radivojkov-Blagojevic Milena M
Lichtner Peter P
Singleton Andrew B AB
Hernandez Dena G DG
Edsall Connor C
Mellick George D GD
Zimprich Alexander A
Pirker Walter W
Rogaeva Ekaterina E
Lang Anthony E AE
Koks Sulev S
Taba Pille P
Lesage Suzanne S
Brice Alexis A
Corvol Jean-Christophe JC
Chartier-Harlin Marie-Christine MC
Mutez Eugénie E
Brockmann Kathrin K
Deutschländer Angela B AB
Hadjigeorgiou Georges M GM
Dardiotis Efthimos E
Stefanis Leonidas L
Simitsi Athina Maria AM
Valente Enza Maria EM
Petrucci Simona S
Duga Stefano S
Straniero Letizia L
Zecchinelli Anna A
Pezzoli Gianni G
Brighina Laura L
Ferrarese Carlo C
Annesi Grazia G
Quattrone Andrea A
Gagliardi Monica M
Matsuo Hirotaka H
Kawamura Yusuke Y
Hattori Nobutaka N
Nishioka Kenya K
Chung Sun Ju SJ
Kim Yun Joong YJ
Kolber Pierre P
van de Warrenburg Bart Pc BP
Bloem Bastiaan R BR
Aasly Jan J
Toft Mathias M
Pihlstrøm Lasse L
Guedes Leonor Correia LC
Ferreira Joaquim J JJ
Bardien Soraya S
Carr Jonathan J
Tolosa Eduardo E
Ezquerra Mario M
Pastor Pau P
Diez-Fairen Monica M
Wirdefeldt Karin K
Pedersen Nancy L NL
Ran Caroline C
Belin Andrea C AC
Puschmann Andreas A
Hellberg Clara C
Clarke Carl E CE
Morrison Karen E KE
Tan Manuela M
Krainc Dimitri D
Burbulla Lena F LF
Farrer Matt J MJ
Krüger Rejko R
Gasser Thomas T
Sharma Manu M
Elbaz Alexis A
Study Outcome
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