Linking ambient air pollution to mental health: evidence based on the two-sample Mendelian randomization and colocalization study

Growing evidence links air pollution, a ubiquitous environmental stressor, to a higher risk of developing mental disorders, raising significant public health concerns. Mental disorders represent a significant global public health challenge which can have a profound impact on individual lives. In this study, we used Mendelian randomization (MR) to investigate the causal relationship between ambient air pollution and four common mental disorders. Genome-wide association study (GWAS) data for ambient air pollution and summary-level GWAS data for four representative mental disorders were obtained from open-access database. Inverse variance weighted (IVW) method with multiplicative random-effects model was the main analysis. Sensitivity analyses were conducted to validate the results. Bayesian colocalization analysis was conducted to explore the potential shared genetic causal variants between specific air pollutants and mental disorders. A suggestive association was observed between political matter (PM) 2.5 and anxiety disorders (OR 2.96, 95%CI 1.29-6.81, p = 0.010). Exposure to nitrogen dioxide (NO2) was significantly linked to an elevated risk of schizophrenia (OR 1.95, 95% CI 1.45-2.63, p = 1.13E-05) and showed a nominal association with an increased risk of bipolar disorder (OR 1.43, 95% CI 1.09-1.86, p = 0.009). A suggestive causal association was detected between nitrogen oxides (NOx) and anxiety disorder (OR 2.90, 95%CI 1.21-6.97, p = 0.017). No significant association was detected between exposure to PM2.5-10, PM10 and mental disorders. No significant horizonal pleiotropy and heterogeneity was found. The colocalization analysis revealed robust evidence supporting the colocalization of NO2 with schizophrenia at SNP rs12203592. Our findings support causal associations between exposure to ambient air pollution, particularly PM2.5, NO₂, and NOx, and an increased risk of specific mental disorders.