Assessing the causal relationship between nitrogen dioxide air pollution and schizophrenia risk: A large-scale Mendelian randomization study

Nitrogen dioxide (NO 2 ) is mainly discharged from the burning of fossil fuels and remains suspended in the air with other particulate pollutants, which has a significant impact on the Earth’s ecological environment and is harmful to human health. Schizophrenia is a nervous system disease involving emotion, thinking, and behavior. There is no consistent conclusion about the etiology of schizophrenia, though numerous studies are ongoing. Previous studies suggest that exposure to NO 2 air pollution may increase the risk of schizophrenia, though this remains in the early exploratory stages. We conducted a 2-sample Mendelian Randomization study to investigate the potential causal effect of NO 2 exposure on schizophrenia risk. Genetic instruments were selected from large-scale genome-wide association studies of European ancestry, including NO 2 exposure (n = 456,380) and schizophrenia (n = 640,808). To ensure the reliability of our findings, we also conducted sensitivity analyses. Across all Mendelian Randomization models, NO 2 exposure showed a significant positive causal effect on schizophrenia risk. Beta values ranged from 0.246 (weighted median estimator model, 102 single nucleotide polymorphisms) to 0.478 (inverse variance weighting model, 128 single nucleotide polymorphisms), with all P < .05. odds ratios ranged from 1.30 (95% confidence interval: 1.03–1.65, weighted median estimator, exposure: ukb-b-9942; outcome: ieu-b-5099) to 1.60 (95% confidence interval: 1.39–1.87, inverse variance weighting fixed effects, exposure: ukb-b-5620; outcome: ieu-b-5099). Sensitivity analyses and heterogeneity tests confirmed the robustness of these findings. These findings help further our understanding of the etiology of schizophrenia and provide a new perspective for air pollution mitigation.