Air Pollution and Genetics: A Dangerous Duo for Parkinson's Risk, Study Finds

"Individuals with high polygenic risk scores and elevated residential carbon monoxide levels faced a threefold increase in PD risk (OR 3.05), emphasizing air pollution as a critical modifiable factor, particularly for those with genetic vulnerability," the researchers reported in JAMA Network Open.

Parkinson’s disease is a progressive neurodegenerative disorder that affects movement and cognition. While genetics has long been known to play a role in its development, growing evidence suggests that environmental factors, such as air pollution, may act as triggers or accelerators of the disease. However, the influence of genetic susceptibility on the link between traffic-related air pollution (TRAP) and Parkinson’s disease is not yet fully understood.

To fill this knowledge gap, Dayoon Kwon, Department of Epidemiology, Fielding School of Public Health, UCLA (University of California, Los Angeles), Los Angeles, and colleagues aimed to evaluate the interaction between the polygenic risk score (PRS) for PD and prolonged exposure to TRAP to determine their combined impact on PD risk.

For this purpose, the researchers conducted a population-based case-control study using data from central California and Denmark. The analysis included 634 Parkinson’s disease patients and 733 controls from the Parkinson Environment and Genes (PEG) study and 966 PD patients and 1045 controls from the Parkinson's Disease in Denmark (PASIDA) study. Genetic susceptibility was assessed using a polygenic risk score, while long-term traffic-related air pollution exposure was estimated through dispersion models, focusing on carbon monoxide levels near residences. Multivariable logistic regression assessed the interaction between PRS and TRAP exposure, evaluating their combined impact on PD risk.

Key Findings:

• The study included 1,600 patients with Parkinson’s disease (PD) (mean age: 65.1 years; 61.9% male) and 1,778 controls (mean age: 64.5 years; 55.8% male).
• Both a higher polygenic risk score (PRS) and increased traffic-related air pollution (TRAP) exposure were associated with a greater risk of PD.
• The interaction effect estimate between PRS and TRAP exposure was 1.06.
• Individuals with both high PRS and high TRAP exposure had the highest PD risk (odds ratio: 3.05) compared to those with low PRS and low TRAP exposure, indicating a synergistic effect.

These findings highlight the combined impact of genetic susceptibility and long-term exposure to traffic-related air pollution on Parkinson’s disease risk. While genetic predisposition influences a subset of individuals, TRAP remains a widespread modifiable risk factor affecting large populations globally.

"The study highlights the need for further research to validate these results and explore the biological mechanisms underlying this interaction. Reducing air pollution exposure could be a crucial preventive strategy, particularly for those with a genetic vulnerability to PD," the authors concluded.

Reference:

Kwon D, Paul KC, Kusters C, et al. Interaction Between Traffic-Related Air Pollution and Parkinson Disease Polygenic Risk Score. JAMA Netw Open. 2025;8(3):e250854. doi:10.1001/jamanetworkopen.2025.0854