Risky behaviour link with PD: genetic or environmental factors?

Movement disorders

By Mardi Chapman

20 Sep 2019

A genetic tendency-to-smoke trait is possibly causally related to Parkinson disease (PD), with individuals who started smoking being protected against PD.

According to a study published in Neurology, other risky behaviour phenotypes might also be inversely associated with the development of PD.

The researchers said their findings are consistent with other observational studies which have shown the inverse association of smoking with PD.

However the challenge in PD has been to “decipher whether these PD-associated environmental/lifestyle/behavioural variables contribute to or are an effect of the disease”.

The study used Mendelian randomisation (MR) to apply 611 independent loci for risky behaviour to data from a genome-wide association study of PD.

The loci came from a discovery cohort of 939,908 individuals of European ancestry with six highly correlated risky behaviour phenotypes, including general risk tolerance, adventurousness, automobile speeding propensity, drinks per week, ever vs never smoking, and number of sexual partners.

The study found a genetically increased risk of tendency to smoke was associated with a reduced risk of PD (OR 0.714 per log odds of ever smoking, 95% confidence interval [CI] 0.568–0.897, p = 0.0041).

“For other risk-taking behaviours, including general risk tolerance, automobile speeding propensity, and the number of sexual partners, we observed a trend toward positive associations (general risk tolerance: OR 1.620 per log odds of general risk tolerance, 95% CI 1.046–2.511, p = 0.0311; automobile speeding propensity: OR 2.043 for each 1-SD increase in normalized automobile speed propensity, 95% CI 1.076–3.876, p = 0.0299; number of sexual partners: OR 1.473 for each 1-SD increase in the number of sexual partners, 95% CI 1.079–2.010, p = 0.0152),” the study authors wrote.

A secondary MR analysis did not show any association of other habitual traits, including other smoking phenotypes such as number of cigarettes per day, cannabis dependence, pathologic gambling, and alcohol and coffee consumption with PD.

The researchers said their findings may assist in differentiating between mediators and exposures, “thereby helping us to construct the causal pathways leading to PD”.

“We further stress the need for interpreting the evidence of causality from our study cautiously in light of existing biological knowledge and further evidence from other epidemiologic study designs.”

An accompanying editorial said MR has a number of strengths such as considering pleiotropy – when one gene mutation apparently influences two unrelated phenotypic traits of disease – avoiding reverse causation and potentially minimising confounders.

“The ability of MR to control for such biases is particularly important for preventing misinterpretation of the data and reducing the error of targeting genetic and environmental risk factors that are not causative of PD.”

It said the study is one of the few attempts to explore traits of possible risky behaviours and the association with PD.

“Therefore, it contributes to the theory that genetic and environmental factors may interact and may be influenced by and can influence risky behaviours. This relationship could, in the long run, lead to a degeneration of the brain, in this case PD.”

“’Livin’ on the edge’ can be considered secondary to a different dopaminergic tone that can be genetically determined but also can be modifiable and have a role in the development of PD and related disorders.”

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