Associations between multiple ambient air pollutants, genetic risk, and incident mental disorders: An interaction study in the UK population

Abstract

Mental disorders can be triggered by genetic and environmental risk factors. Limited studies have explored the effects of long-term exposure to air pollution on mental disorders, and most of the studies have focused on individual air pollutants. This study aimed to examine the relationship between long-term exposure to multiple air pollutants and incident mental disorders, including depression, anxiety, and schizophrenia, and whether the associations were affected by genetic susceptibility. Participants in the UK Biobank with no history of mental disorders were followed from baseline (2006 to 2010) to October 31st, 2022. Cox regression was applied to evaluate the correlation between PM_2.5 absorbance, PM_2.5, PM_2.5-10, PM₁₀, NO₂, and NOx and any or specific mental disorders. Additive and multiplicative scales were used to measure the interaction between air pollution and schizophrenia polygenic risk score (PRS), depression PRS, or anxiety PRS on specific mental diseases. After a median of 13.36 years of follow-up on 252,376 participants, we observed per interquartile increase of PM_2.5 absorbance (0.32 per meter), PM_2.5 (1.28 μg/m³), NO₂ (10.08 μg/m³), and NO_x (16.78 μg/m³) were related to a 2-6 % higher risk of incident mental disorders. The HR (95 % CI) of incident mental disorder for the 2nd, 3rd, and 4th quartile of the air pollution score were 1.05 (1.01-1.18), 1.13 (1.09-1.18), and 1.14 (1.09-1.19), respectively, in comparison to the lowest level of the score. Per interquartile increase in the air pollution score was associated with a 6 %, 24 %, 4 %, and 6 % higher risk of incident mental disorders, schizophrenia, depression, and anxiety, respectively. No interaction between air pollution and genetic risk of schizophrenia, depression or anxiety on corresponding incident disorders was observed. These findings emphasize the importance of implementing air pollution control standards to decrease the burden of mental disorders.

Keywords: Air pollution; Cohort study; Gene-environment interaction; Mental disorder; Polygenic risk score.