Air pollutants, genetic susceptibility, and the risk of age-related macular degeneration: a large prospective cohort study

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. However, evidence regarding the relationship between air pollution and AMD is limited, and the modifying effect of genetic susceptibility on this association remains unknown. A total of 445,237 participants without AMD at baseline were included from the UK Biobank. The concentrations of nitrogen dioxide (NO 2 ), nitrogen oxides (NO x ), particulate matter (PM 2.5 , PM 10 , PM 2.5−10 ) were collected by using land-use regression models. Air pollution score (APS) was constructed through summing each pollutant weighted by the regression coefficients with AMD from single-pollutant model. Cox proportional hazard models were used to evaluate hazard rations (HRs) and 95% confidence intervals (95%CIs) of associations between air pollutants and polygenic risk score (PRS) with incident AMD. During a median follow-up of 13.83 years, we observed 9,635 incident AMD events. The HR (95%CI) of incident AMD for each standard deviation increase in NO 2 , NO x , PM 2.5 , PM 10 , and APS were 1.04(1.02, 1.06), 1.03(1.01, 1.05). 1.04(1.02, 1.07), 1.02(1.00, 1.04), and 1.04(1.02, 1.06), respectively. Significant additive interaction effects of NO 2 , NO x , PM 2.5−10 , APS and PRS with incident risk of AMD were observed, with the relative excess risk due to the interaction (RERI), attributable proportion (AP), and their 95% CIs of 0.10(0.01, 0.18) and 0.05(0.01, 0.11) for NO 2 , 0.11(0.01, 0.19) and 0.05(0.02, 0.10) for NO x , 0.15(0.06, 0.23) and 0.08(0.03, 0.13) for PM 2.5−10 , and 0.12(0.03, 0.20) and 0.06(0.01, 0.11) for APS, respectively. Compared with participants exposed to low level of above air pollutants and low PRS, those exposed to high air pollution and high PRS had almost double incident risk of AMD [HR(95%CI) ranged from 1.83(1.68, 1.99) to 2.03(1.86, 2.21)]. Long-term exposure to air pollutants NO 2 , NO x , PM 2.5 , and PM 10 showed positive associations with increased risk of AMD, which could be further enhanced by genetic susceptibility.