Joint exposure to multiple air pollutants, genetic risk and incident psoriasis: a large-scale prospective cohort study

BACKGROUND: Air pollution and genetic risk have been found to contribute to the onset and development of psoriasis. However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of incident psoriasis remains unknown. OBJECTIVES: To assess the association between joint exposure to multiple air pollutants and the risk of psoriasis, and its modification, according to genetic susceptibility. METHODS: This prospective study included 451 064 participants from the UK Biobank who had complete air pollution data and were free of psoriasis at baseline. All participants were enrolled from 2006 to 2010 and followed up to 2022. An air pollution score (APS) was calculated to assess joint exposure to multiple air pollutants, including fine particulate matter (PM) with diameters ≤ 2.5 μm (PM2.5), between 2.5 and 10 μm (PM2.5-10) and ≤ 10 μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). To evaluate the genetic risk, a polygenic risk score (PRS) for psoriasis was constructed. Cox proportional hazard models were used to assess the association of air pollution and genetic susceptibility with the risk of psoriasis. Stratified analyses were conducted based on the individual characteristics. RESULTS: During a median follow-up of 13.79 years (range 0.00-16.81), 4414 cases of psoriasis were recorded. The hazard ratios (HRs) for psoriasis were 1.036 [95% confidence interval (CI) 0.936-1.147], 1.091 (95% CI 0.987-1.206), 1.159 (95% CI 1.048-1.283) and 1.163 (95% CI 1.052-1.286) in the higher APS quintile groups (Q2, Q3, Q4 and Q5, respectively) vs. the lowest APS quintile (Q1; P-value for trend < 0.05). When considering genetic susceptibility, participants with a high PRS and a high APS had the greatest risk of incident psoriasis (HR 1.962, 95% CI 1.630-2.362) vs. those with a low PRS and low APS. The HRs for PM2.5-10, NOx, PM2.5 absorbance, PM2.5, NO2 and PM10 in the group with the highest exposure level and genetic risk were 1.831 (95% CI 1.537-2.181), 1.722 (95% CI 1.431-2.073), 1.698 (95% CI 1.416-2.037), 1.619 (95% CI 1.353-1.938), 1.504 (95% CI 1.252-1.806) and 1.425 (95% CI 1.192-1.704), respectively. CONCLUSIONS: Long-term exposure to various air pollutants is positively associated with an increased risk of incident psoriasis, particularly in individuals with a high genetic risk of the disease. More comprehensive measures are needed to reduce the air pollution levels for better prevention of psoriasis.