Air pollutants, genetic susceptibility and the risk of schizophrenia: large prospective study.

Background: Evidence linking air pollutants and the risk of schizophrenia remains limited and inconsistent, and no studies have investigated the joint effect of air pollutant exposure and genetic factors on schizophrenia risk.

Aims: To investigate how exposure to air pollution affects schizophrenia risk and the potential effect modification of genetic susceptibility.

Method: Our study was conducted using data on 485 288 participants from the UK Biobank. Cox proportional hazards models were used to estimate the schizophrenia risk as a function of long-term air pollution exposure presented as a time-varying variable. We also derived the schizophrenia polygenic risk score (PRS) utilising data provided by the UK Biobank, and investigated the modification effect of genetic susceptibility.

Results: During a median follow-up period of 11.9 years, 417 individuals developed schizophrenia (mean age 55.57 years, s.d. = 8.68; 45.6% female). Significant correlations were observed between long-term exposure to four air pollutants (PM_2.5; PM₁₀; nitrogen oxides, NO_x; nitrogen dioxide, NO₂) and the schizophrenia risk in each genetic risk group. Interactions between genetic factors and the pollutants NO₂ and NO_x had an effect on schizophrenia events. Compared with those with low PRS and low air pollution, participants with high PRS and high air pollution had the highest risk of incident schizophrenia (PM_2.5: hazard ratio = 6.25 (95% CI 5.03-7.76); PM₁₀: hazard ratio = 7.38 (95% CI 5.86-9.29); NO₂: hazard ratio = 6.31 (95% CI 5.02-7.93); NO_x: hazard ratio = 6.62 (95% CI 5.24-8.37)).

Conclusions: Long-term exposure to air pollutants was positively related to the schizophrenia risk. Furthermore, high genetic susceptibility could increase the effect of NO₂ and NO_x on schizophrenia risk.