Background: Accumulating research has linked ambient air pollution exposure to alterations in cortical surface area (SA) and thickness; howe
Background: Accumulating research has linked ambient air pollution exposure to alterations in cortical surface area (SA) and thickness; however, the causal inferences remain controversial. Our investigation aims to determine the causality between air pollution and brain cortical morphology using the Mendelian randomization (MR) approach. Methods: Public accessible genome-wide association studies data on particulate matter 2.5 (PM2.5), PM2.5 absorbance, PM10, PM2.5–10, nitrogen dioxide (NO2), and nitrogen oxides (NOX) concentration were screened to select instrumental variables. Univariable MR (UVMR) was performed to assess the causality of air pollution on brain cortical structure using five MR methods. Multivariable MR (MVMR) was further conducted to strengthen the robustness of the identified relationships by adjusting for related pollutant phenotypes, household income, and unhealthy eating habits. Results: The UVMR analysis identified fourteen causal associations between air pollution susceptibility and alterations in brain cortical morphology, with nine showing negative effects and five showing positive effects concurrently. The MVMR models indicated negative causal relationships between PM2.5 level and the SA of the inferior temporal cortex (beta [95 %CI] = -215.739 [-404.284 to -27.194], p = 0.025), NO2 level and the SA of the lateral occipital cortex (beta [95 %CI] = -548.577 [-1086.450 to -10.699], p = 0.046), and a positive correlation between PM2.5 absorbance and SA of the bankssts cortex (beta [95 %CI] = 76.491 [14.267–138.716], p = 0.016). No evidence of heterogeneity or pleiotropy was noticed. Conclusions: Our exploration established causal relationships between air pollution exposure and brain cortical structure, underscoring the significance of mitigating air pollution to preserve brain cortical morphology.
