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Neurology. 2019 Oct 8;93(15):e1412-e1424. doi: 10.1212/WNL.0000000000008245. Epub 2019 Sep 16.

Risky behaviors and Parkinson disease: A mendelian randomization study.

Author information

1
From the Institut für Medizinische Biometrie und Statistik (S.G., I.R.K.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Genetic and Molecular Epidemiology Group (C.M.L.), Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, Institute of Neurogenetics (M.K.), Department of Psychiatry and Psychotherapy, and Institute of Neurogenetics (C.K.), Universität zu Lübeck, Germany; and Institute for Biomedicine (F.D.G.M.), Eurac Research, Bolzano, Italy.
2
From the Institut für Medizinische Biometrie und Statistik (S.G., I.R.K.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Genetic and Molecular Epidemiology Group (C.M.L.), Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, Institute of Neurogenetics (M.K.), Department of Psychiatry and Psychotherapy, and Institute of Neurogenetics (C.K.), Universität zu Lübeck, Germany; and Institute for Biomedicine (F.D.G.M.), Eurac Research, Bolzano, Italy. inke.koenig@imbs.uni-luebeck.de fabiola.delgreco@eurac.edu.

Abstract

OBJECTIVE:

To examine causal associations between risky behavior phenotypes and Parkinson disease using a mendelian randomization approach.

METHODS:

We used 2-sample mendelian randomization to generate unconfounded estimates using summary statistics from 2 independent, large meta-analyses of genome-wide association studies on risk-taking behaviors (n = 370,771-939,908) and Parkinson disease (cases n = 9,581, controls n = 33,245). We used the inverse variance weighted method as the main method for judging causality.

RESULTS:

Our results support a strong protective association between the tendency to smoke and Parkinson disease (odds ratio [OR] 0.714 per log odds of ever smoking, 95% confidence interval [CI] 0.568-0.897, p = 0.0041, Cochran Q test p = 0.238; I 2 index 6.3%). Furthermore, we observed risk association trends between automobile speed propensity and the number of sexual partners and Parkinson disease after removal of overlapping loci with other risky traits (OR 1.986 for each 1-SD increase in normalized automobile speed propensity, 95% CI 1.215-3.243, p = 0.0066; OR 1.635 for each 1-SD increase in number of sexual partners, 95% CI 1.165-2.293, p = 0.0049).

CONCLUSION:

These findings provide support for a causal relationship between general risk tolerance and Parkinson disease and may provide new insights into the pathogenic mechanisms leading to the development of Parkinson disease.

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