Air pollutants, genetic susceptibility, and incident schizophrenia in later life: A prospective study in the UK Biobank

Objective: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late -onset schizophrenia and evaluate whether genetic susceptibility could modify the association. Methods: This population -based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO 2 ), nitrogen oxides (NO x ), fine particulate matter (PM 2.5 ), and inhalable particulate matter (PM 10 ) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. Results: An interquartile range increase in PM 2.5 , PM 10 , NO 2 , and NO x was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure -response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM 10 , NO 2 , and NO x with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. Conclusion: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late -onset schizophrenia in an aging era, especially among those with high genetic risks.