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Domenighetti, C.* ; Sugier, P.E.* ; Sreelatha, A.A.K.* ; Schulte, C.* ; Grover, S.* ; Mohamed, O.* ; Portugal, B.* ; May, P.* ; Bobbili, D.R.* ; Radivojkov-Blagojevic, M. ; Lichtner, P. ; Singleton, A.B.* ; Hernandez, D.G.* ; Edsall, C.* ; Mellick, G.D.* ; Zimprich, A.* ; Pirker, W.* ; Rogaeva, E.* ; Lang, A.E.* ; Kõks, S.* ; Taba, P.* ; Lesage, S.* ; Brice, A.* ; Corvol, J.C.* ; Chartier-Harlin, M.C.* ; Mutez, E.* ; Brockmann, K.* ; Deutschländer, A.B.* ; Hadjigeorgiou, G.M.* ; Dardiotis, E.* ; Stefanis, L.* ; Simitsi, A.M.* ; Valente, E.M.* ; 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.J.* ; Kim, Y.J.* ; Kolber, P.* ; van de Warrenburg, B.P.* ; Bloem, B.R.* ; Aasly, J.O.* ; Toft, M.F.* ; Pihlstrm, L.* ; Guedes, L.C.* ; Ferreira, J.J.* ; Bardien, S.* ; Carr, J.A.* ; Tolosa, E.* ; Ezquerra, M.* ; Pastor, P.* ; Diez-Fairen, M.* ; Wirdefeldt, K.* ; Pedersen, N.L.* ; Ran, C.* ; Belin, A.C.* ; Puschmann, A.J.* ; Hellberg, C.* ; Clarke, C.E.* ; Morrison, K.E.* ; Tan, M.* ; Krainc, D.* ; Burbulla, L.F.* ; Farrer, M.J.* ; Krüger, R.* ; Gasser, T.* ; Sharma, M.* ; Elbaz, A.*

Mendelian randomisation study of smoking, alcohol, and coffee drinking in relation to parkinson's disease.

J. Parkinsons Dis. 12, 267-282 (2022)
Postprint Research data DOI PMC
Open Access Gold
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Parkinson’s Disease ; Smoking ; Alcohol ; Coffee ; Mendelian Randomisation; Risk-factors; Transdermal Nicotine; Pooled Analysis; Metaanalysis; Instruments; Pd
Language english
Publication Year 2022
Prepublished in Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1877-7171
e-ISSN 1877-718X
Journal Journal of Parkinson's disease
Quellenangaben Volume: 12, Issue: 1, Pages: 267-282 Article Number: , Supplement: ,
Publisher IOS Press
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
Grants UK Medical Research Council (CEC, KEM)
NRF-DST Centre of Excellence for Biomedical Tuberculosis Research
Stellenbosch University, South Africa
South African Medical Research Council (Self-Initiated Research Grant)
National Research Foundation of South Africa
Italian Ministry of Health (Ricerca Corrente 2021)
Estonian Research Council
MSWA
Canadian Consortium on Neurodegeneration in Aging
Department of Health and Human Services
Intramural Research Program of the National Institute on Aging
Michael J Fox Foundation (USA Genetic Diversity in PD Program: GAP-India)
MSA Coalition
German Research Council
South African Medical Research Council Centre for Tuberculosis Research
Division of Molecular Biology and Human Genetics
Faculty of Medicine and Health Sciences
Parkinson's UK. PG GEN sample collection - MRC
Karolinska Institutet Research Funds
Karolinska Institutet Research Fund
Swedish Brain Foundation
Marta Lundkvist Foundation
National Institutes of Health
Swedish Research Council
Spanish Ministry of Science and Innovation
Cape Town
Stellenbosch University
EU Joint Program for Neurodegenerative Disease research (JPND)
DOI 10.3233/JPD-212851
WOS ID WOS:000747072700020
Scopus ID 85123813753
PubMed ID 34633332
Erfassungsdatum 2021-12-06
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