Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Domenighetti C

PROVIDER: S-EPMC9211765 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

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

Journal of Parkinson's disease 20220101 1

<h4>Background</h4>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.<h4>Objective</h4>To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases.<h4>Methods</h4>We used summary statistics fro ...[more]

PMID: 34633332

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Project description:BackgroundClozapine is an effective antipsychotic medication for patients with treatment-resistant schizophrenia. Previous studies revealed that smoking, alcohol intake, and coffee consumption altered the metabolism of clozapine. However, causal associations between substance use and clozapine levels were not sufficiently established.MethodsSeveral genome-wide association studies provided genetic tools for six measures of substance use, including age of smoking, cigarettes per day, smoking cessation, smoking initiation, coffee consumption, and alcohol consumption (GWASs). Utilizing the CLOZUK consortium's dataset, their associations with clozapine and its metabolite concentrations were evaluated. All GWAS data were collected from the European population. Mendelian randomization (MR) estimations from each genetic test were combined using inverse variance weighted (IVW) meta-analysis in combination with complementing techniques (such as weighted median and MR Egger). We also analyze horizontal pleiotropy and heterogeneity using various sensitivity analyses.ResultsGenetically predicted higher level of smoking initiation was significantly associated with reduced clozapine (β = -0.14, P = 4.53E-04) concentrations and norclozapine concentrations (β = -0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations (β = -0.42, P = 1.70E-14), norclozapine concentrations (β = -0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine (β = -0.15, P = 5.35E-07), survived after the Bonferroni correction (P = 0.05/6 = 0.008). In sensitivity analyses, the weighted median and MR Egger methods demonstrated directionally consistent effects. In addition, our sensitive test indicated no significant horizontal pleiotropy and heterogeneity (P > 0.05). However, other measures of substance use (age of initiation smoking, cigarettes per day, smoking cessation, and drinks per week) were not associated with clozapine metabolism.ConclusionOur investigation revealed a correlation between greater smoking initiation and coffee consumption and reduced blood levels of clozapine and norclozapine. Providing clinicians with guidance on how to adjust clozapine levels for clozapine-treated patients.

Project description:BackgroundSmoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers.Methods and findingsWe used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.59-2.03; p = 2.26 × 10-21) and UK Biobank (OR 2.26; 95% CI 1.92-2.65; p = 1.17 × 10-22). Additionally, genetic predisposition to smoking was associated with statistically significant higher odds of cancer of the oesophagus (OR 1.83; 95% CI 1.34-2.49; p = 1.31 × 10-4), cervix (OR 1.55; 95% CI 1.27-1.88; p = 1.24 × 10-5), and bladder (OR 1.40; 95% CI 1.92-2.65; p = 9.40 × 10-5) and with statistically nonsignificant higher odds of head and neck (OR 1.40; 95% CI 1.13-1.74; p = 0.002) and stomach cancer (OR 1.46; 95% CI 1.05-2.03; p = 0.024). In contrast, there was an inverse association between genetic predisposition to smoking and prostate cancer in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (OR 0.90; 95% CI 0.83-0.98; p = 0.011) and in UK Biobank (OR 0.90; 95% CI 0.80-1.02; p = 0.104), but the associations did not reach statistical significance. We found no statistically significant association between genetically predicted alcohol consumption and overall cancer (n = 75,037 cases; OR 0.95; 95% CI 0.84-1.07; p = 0.376). Genetically predicted alcohol consumption was statistically significantly associated with lung cancer in the International Lung Cancer Consortium (OR 1.94; 95% CI 1.41-2.68; p = 4.68 × 10-5) but not in UK Biobank (OR 1.12; 95% CI 0.65-1.93; p = 0.686). There was no statistically significant association between alcohol consumption and any other site-specific cancer. The main limitation of this study is that precision was low in some analyses, particularly for analyses of alcohol consumption and site-specific cancers.ConclusionsOur findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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