TY - JOUR
T1 - Mendelian randomisation study of smoking, alcohol, and coffee drinking in relation to Parkinson's disease
AU - Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium
AU - Domenighetti, Cloé
AU - Sugier, Pierre-Emmanuel
AU - Sreelatha, Ashwin Ashok Kumar
AU - Schulte, Claudia
AU - Grover, Sandeep
AU - Mohamed, Océane
AU - Portugal, Berta
AU - May, Patrick
AU - Bobbili, Dheeraj R
AU - Radivojkov-Blagojevic, Milena
AU - Lichtner, Peter
AU - Singleton, Andrew B
AU - Hernandez, Dena G
AU - Edsall, Connor
AU - Mellick, George D
AU - Zimprich, Alexander
AU - Pirker, Walter
AU - Rogaeva, Ekaterina
AU - Lang, Anthony E
AU - Koks, Sulev
AU - Taba, Pille
AU - Lesage, Suzanne
AU - Brice, Alexis
AU - Corvol, Jean-Christophe
AU - Chartier-Harlin, Marie-Christine
AU - Mutez, Eugénie
AU - Brockmann, Kathrin
AU - Deutschländer, Angela B
AU - Hadjigeorgiou, Georges M
AU - Dardiotis, Efthimos
AU - Stefanis, Leonidas
AU - Simitsi, Athina Maria
AU - Valente, Enza Maria
AU - Petrucci, Simona
AU - Duga, Stefano
AU - Straniero, Letizia
AU - Zecchinelli, Anna
AU - Pezzoli, Gianni
AU - Brighina, Laura
AU - Ferrarese, Carlo
AU - Annesi, Grazia
AU - Quattrone, Andrea
AU - Gagliardi, Monica
AU - Matsuo, Hirotaka
AU - Kawamura, Yusuke
AU - Hattori, Nobutaka
AU - Nishioka, Kenya
AU - Chung, Sun Ju
AU - Kim, Yun Joong
AU - Clarke, Carl E
PY - 2021/10/7
Y1 - 2021/10/7
N2 - 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.
AB - 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.
KW - Smoking
KW - alcohol
KW - coffee
KW - Parkinson’s disease
KW - Mendelian randomisation
U2 - 10.3233/JPD-212851
DO - 10.3233/JPD-212851
M3 - Article
C2 - 34633332
SN - 1877-7171
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
ER -