Abstract
BACKGROUND AND AIM[|]Although environmental and genetic factors have been linked to Parkinson’s disease (PD), the influence of genetic susceptibility on the association between long-term exposure to traffic-related air pollution and PD is not well understood.[¤]METHOD[|]Our case-control analysis included 664 PD and 733 population controls, who also provided blood samples. We estimated annual average traffic-related air pollutant concentrations (represented by carbon monoxide; CO) at residential and workplace locations from 1981 to 2016 using the California Line Source Dispersion Model version 4. Long-term exposures were calculated as 10-year averages with a 5-year lag time prior to a PD diagnosis for cases and the interview date for controls and we categorized it as high/low using a median cut. A polygenic risk score (PRS) was computed by summing the effect estimates of well-known risk alleles from existing genome-wide association studies (GWAS) summary statistics with data from individuals genetic array to assess individual genetic risks for PD. Logistic regression models were employed to estimate odds ratios (OR) and 95% confidence interval (CI), adjusting for age, race, sex, education, and study wave, for the effect of genetic risk on the association between air pollution exposure and PD risk.[¤]RESULTS[|]The OR for PD among individuals with high PD-PRS risk (> median) and high CO exposure (> median) at residences was 2.55 (95% CI: 1.86, 3.48) and 3.62 (2.11, 6.18) at workplaces compared to individuals with low PD-PRS and low CO. Gene-environment interactions were observed on a multiplicative scale (p = 0.05) at residential locations.[¤]CONCLUSIONS[|]Our findings suggest that a combination of long-term exposure to air pollution from traffic and genetic susceptibility contributes to the risk of developing PD.[¤]