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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Autores principales: Carmen Domínguez-Baleón, Jue-Sheng Ong, Clemens R. Scherzer, Miguel E. Rentería, Xianjun Dong
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Publicado: Nature Portfolio 2021
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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