Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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

J Parkinsons Dis. 2022;12(1):267-282.

Authors/Editors: Domenighetti C
Sugier PE
Sreelatha AAK
Schulte C
Grover S
Mohamed O
Portugal B
May P
Bobbili DR
Radivojkov-Blagojevic M
Lichtner P
Singleton AB
Hernandez DG
Edsall C
Mellick GD
Zimprich A
Pirker W
Rogaeva E
Lang AE
Koks S
Taba P
Lesage S
Brice A
Corvol JC
Chartier-Harlin MC
Mutez E
Brockmann K
Deutschländer AB
Hadjigeorgiou GM
Dardiotis E
Stefanis L
Simitsi AM
Valente EM
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 SJ
Kim YJ
Kolber P
van de Warrenburg BP
Bloem BR
Aasly J
Toft M
Pihlstrøm L
Guedes LC
Ferreira JJ
Bardien S
Carr J
Tolosa E
Ezquerra M
Pastor P
Diez-Fairen M
Wirdefeldt K
Pedersen NL
Ran C
Belin AC
Puschmann A
Hellberg C
Clarke CE
Morrison KE
Tan M
Krainc D
Burbulla LF
Farrer MJ
Krüger R
Gasser T
Sharma M
Elbaz A
Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium
Publication Date: 2022
Type of Publication: Journal Article


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.

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