Joint effects of air pollution and genetic susceptibility on incident primary open-angle glaucoma

Background: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG.

Methods: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale.

Results: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM_2.5, PM_2.5 absorbance, PM₁₀, NO₂, and NO_X individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM_2.5 absorbance and NO₂ in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly.

Conclusion: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.