Long-term exposure to fine particulate matter and its constituents, genetic susceptibility, and incident bipolar...

To date, research on the relationship between long-term exposure to PM_2.5 constituents and the risk of bipolar disorder (BD) remains underexplored. This study investigated this association using data from 495,139 participants in the UK Biobank. Daily average concentrations of PM_2.5 constituents from 2006 to 2020 were estimated using the European Monitoring and Evaluation Program model applied to the UK (EMEP4UK). Time-weighted Cox proportional hazards models were employed to quantify the risk of BD associated with long-term exposure to PM_2.5 and its constituents, while the Quantile g-computation model was used to identify the mixture effects and the key contributing constituent. Furthermore, polygenic risk scores for BD were used to explore gene-environment interactions and joint effects. Over a median follow-up period of 11.90 years, 1,040 newly diagnosed BD cases were detected. PM_2.5 and its constituents were associated with BD risk. After adjustment, the hazard ratios for BD risk per interquartile range increase in each constituent, along with their 95% confidence intervals were as follows: 1.58 (1.47, 1.69) for PM_2.5, 1.38 (1.28, 1.48) for elemental carbon (EC), 1.10 (1.02, 1.18) for organic matter (OM), 1.44 (1.41, 1.48) for ammonium (NH₄⁺), 1.27 (1.18, 1.36) for nitrate (NO₃^-), and 1.26 (1.25, 1.28) for sulfate (SO₄^2-). EC emerged as the primary risk contributor. We also observed both interactive and joint effects of PM_2.5 constituents and genetic susceptibility on BD incidence. These findings underscore the importance of reducing specific PM_2.5 constituents and considering genetic predisposition in public health strategies.