PT  - JOURNAL ARTICLE
AU  - Grover, Sandeep
AU  - Fabiola Del, Greco M
AU  - Kasten, Meike
AU  - Klein, Christine
AU  - Lill, Christina M.
AU  - König, Inke R.
TI  - Risky behaviors and Parkinson’s disease: A Mendelian randomization study in up to 1 million study participants
AID  - 10.1101/446807
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 446807
4099  - http://biorxiv.org/content/early/2018/11/02/446807.short
4100  - http://biorxiv.org/content/early/2018/11/02/446807.full
AB  - Objective Dopaminergic neurotransmission is known to be a potential modulator of risky behaviors including substance abuse, promiscuity, and gambling. Furthermore, observational studies have shown associations between risky behaviors and Parkinson’s disease; however, the causal nature of these associations remains unclear. Thus, in this study, we examine causal associations between risky behavior phenotypes on Parkinson’s disease using a Mendelian randomization approach.Methods We used two-sample Mendelian randomization to generate unconfounded estimates using summary statistics from two independent, large meta-analyses of genome-wide association studies on risk taking behaviors (n=370,771-939,908) and Parkinson’s disease (cases: n=9581, controls: n = 33,245). We used inverse variance weighted as the main method for judging causality.Results Our results support a strong protective association between the tendency to smoke and Parkinson’s disease (OR=0.714 per log odds of ever smoking; 95% CI=0.568-0.897; p-value=0.0041; Cochran Q test; p-value=0.238; I2 index=6.3%). Furthermore, we observed risk association trends between automobile speed propensity as well as the number of sexual partners and Parkinson’s disease after removal of overlapping loci with other risky traits (OR=1.986 for each standard deviation increase in normalized automobile speed propensity; 95% CI=1.215-3.243; p-value=0.0066, OR=1.635 for each standard deviation increase in number of sexual partners; 95% CI=1.165-2.293; p-value=0.0049).Interpretation These findings provide support for a causal relationship between general risk tolerance and Parkinson’s disease and may provide new insights in the pathogenic mechanisms leading to the development of Parkinson’s disease.