Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study
Abstract Previous observational studies have identified correlations between Parkinson’s disease (PD) risk and lifestyle factors. However, whether or not those associations are causal remains unclear. To infer causality between PD risk and smoking or alcohol intake, we conducted a two-sample Mendeli...
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2021
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oai:doaj.org-article:d5332b35691d4aecb36f96d210ba760a2021-12-02T16:14:55ZUnderstanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study10.1038/s41598-021-93105-y2045-2322https://doaj.org/article/d5332b35691d4aecb36f96d210ba760a2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93105-yhttps://doaj.org/toc/2045-2322Abstract Previous observational studies have identified correlations between Parkinson’s disease (PD) risk and lifestyle factors. However, whether or not those associations are causal remains unclear. To infer causality between PD risk and smoking or alcohol intake, we conducted a two-sample Mendelian randomization study using genome-wide association study summary statistics from the GWAS & Sequencing Consortium of Alcohol and Nicotine use study (1.2 million participants) and the latest meta-analysis from the International Parkinson’s Disease Genomics Consortium (37,688 PD cases and 18,618 proxy-cases). We performed sensitivity analyses, including testing for pleiotropy with MR-Egger and MR-PRESSO, and multivariable MR modeling to account for the genetic effects of competing substance use traits on PD risk. Our results revealed causal associations of alcohol intake (OR 0.79; 95% CI 0.65–0.96; p = 0.021) and smoking continuation (which compares current vs. former smokers) (OR 0.64; 95% CI 0.46–0.89; p = 0.008) with lower PD risk. Multivariable MR analyses showed that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior. Finally, frailty analyses suggested that the causal effects of both alcohol intake and smoking continuation on PD risk estimated from MR analysis are not explained by the presence of survival bias alone. Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers. Similarly, increased alcohol intake had a protective effect over PD risk, with the alcohol dehydrogenase 1B (ADH1B) locus as a potential candidate for further investigation of the mechanisms underlying this association.Carmen Domínguez-BaleónJue-Sheng OngClemens R. ScherzerMiguel E. RenteríaXianjun DongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Carmen Domínguez-Baleón Jue-Sheng Ong Clemens R. Scherzer Miguel E. Rentería Xianjun Dong Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
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Abstract Previous observational studies have identified correlations between Parkinson’s disease (PD) risk and lifestyle factors. However, whether or not those associations are causal remains unclear. To infer causality between PD risk and smoking or alcohol intake, we conducted a two-sample Mendelian randomization study using genome-wide association study summary statistics from the GWAS & Sequencing Consortium of Alcohol and Nicotine use study (1.2 million participants) and the latest meta-analysis from the International Parkinson’s Disease Genomics Consortium (37,688 PD cases and 18,618 proxy-cases). We performed sensitivity analyses, including testing for pleiotropy with MR-Egger and MR-PRESSO, and multivariable MR modeling to account for the genetic effects of competing substance use traits on PD risk. Our results revealed causal associations of alcohol intake (OR 0.79; 95% CI 0.65–0.96; p = 0.021) and smoking continuation (which compares current vs. former smokers) (OR 0.64; 95% CI 0.46–0.89; p = 0.008) with lower PD risk. Multivariable MR analyses showed that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior. Finally, frailty analyses suggested that the causal effects of both alcohol intake and smoking continuation on PD risk estimated from MR analysis are not explained by the presence of survival bias alone. Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers. Similarly, increased alcohol intake had a protective effect over PD risk, with the alcohol dehydrogenase 1B (ADH1B) locus as a potential candidate for further investigation of the mechanisms underlying this association. |
format |
article |
author |
Carmen Domínguez-Baleón Jue-Sheng Ong Clemens R. Scherzer Miguel E. Rentería Xianjun Dong |
author_facet |
Carmen Domínguez-Baleón Jue-Sheng Ong Clemens R. Scherzer Miguel E. Rentería Xianjun Dong |
author_sort |
Carmen Domínguez-Baleón |
title |
Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
title_short |
Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
title_full |
Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
title_fullStr |
Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
title_full_unstemmed |
Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study |
title_sort |
understanding the effect of smoking and drinking behavior on parkinson's disease risk: a mendelian randomization study |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/d5332b35691d4aecb36f96d210ba760a |
work_keys_str_mv |
AT carmendominguezbaleon understandingtheeffectofsmokinganddrinkingbehavioronparkinsonsdiseaseriskamendelianrandomizationstudy AT jueshengong understandingtheeffectofsmokinganddrinkingbehavioronparkinsonsdiseaseriskamendelianrandomizationstudy AT clemensrscherzer understandingtheeffectofsmokinganddrinkingbehavioronparkinsonsdiseaseriskamendelianrandomizationstudy AT miguelerenteria understandingtheeffectofsmokinganddrinkingbehavioronparkinsonsdiseaseriskamendelianrandomizationstudy AT xianjundong understandingtheeffectofsmokinganddrinkingbehavioronparkinsonsdiseaseriskamendelianrandomizationstudy |
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