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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5332b35691d4aecb36f96d210ba760a
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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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Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study

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