Both genetics and ambient air pollutants contribute to depression, but the degree to which genetic susceptibility modifies the effect of air pollution on depression remains unknown. We aimed to investigate the effect of the modification of genetic susceptibility on depression. Notably, 490,780 participants who were free of depression at baseline in the UK Biobank study were recruited from 2006 to 2010. A land use regression (LUR) model was performed to estimate the concentrations of particulate matter with diameters ranging from ≤2.5-≤10 μm (PM2.5, PM2.5-10 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx). The International Classification of Diseases 10th Revision (ICD-10) code was used to identify depression cases. Cox proportional hazard models adjusted for covariates were used to investigate the association between ambient air pollutants and depression. Moreover, the polygenic risk score (PRS) was calculated to evaluate cumulative genetic effects, and additive interaction models were established to explore whether genetic susceptibility modified the effects of air pollutants on depression. PM2.5, PM10, NO2 and NOx exposure were significantly positively associated with the risk of depression, and the hazard ratios and 95 % confidence intervals for a 10-μg/m3 increase in PM2.5, PM10, NO2 and NOx concentrations were 2.12 (1.82, 2.47), 1.12 (1.03, 1.23), 1.07 (1.05, 1.10) and 1.04 (1.03, 1.05), respectively. Air pollutants and genetic variants exerted significant additive effects on the risk of depression (relative excess risk due to the interaction [RERI]: 0.15 for PM2.5, 0.12 for PM10, 0.10 for NO2, and 0.12 for NOx; attributable proportion due to the interaction [AP]: 0.12 for PM2.5, 0.10 for PM10, 0.08 for NO2, and 0.09 for NOx). Air pollution exposure was significantly associated with the risk of depression, and participants with a higher genetic risk were more likely to develop depression when exposed to high levels of air pollution.
Keywords: Air pollution; Depression; Genetic susceptibility; Gene–environment interaction; Prospective cohort study.
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