Exposure to Air Pollution, Genetic Susceptibility, and Psoriasis Risk in the UK

Abstract

Importance: Psoriasis is a common autoinflammatory disease influenced by complex interactions between environmental and genetic factors. The influence of long-term air pollution exposure on psoriasis remains underexplored.

Objective: To examine the association between long-term exposure to air pollution and psoriasis and the interaction between air pollution and genetic susceptibility for incident psoriasis.

Design, setting, and participants: This prospective cohort study used data from the UK Biobank. The analysis sample included individuals who were psoriasis free at baseline and had available data on air pollution exposure. Genetic analyses were restricted to White participants. Data were analyzed between November 1 and December 10, 2023.

Exposures: Exposure to nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter with a diameter less than 2.5 µm (PM2.5), and particulate matter with a diameter less than 10 µm (PM10) and genetic susceptibility for psoriasis.

Main outcomes and measures: To ascertain the association of long-term exposure to NO2, NOx, PM2.5, and PM10 with the risk of psoriasis, a Cox proportional hazards model with time-varying air pollution exposure was used. Cox models were also used to explore the potential interplay between air pollutant exposure and genetic susceptibility for the risk of psoriasis incidence.

Results: A total of 474 055 individuals were included, with a mean (SD) age of 56.54 (8.09) years and 257 686 (54.36%) female participants. There were 9186 participants (1.94%) identified as Asian or Asian British, 7542 (1.59%) as Black or Black British, and 446 637 (94.22%) as White European. During a median (IQR) follow-up of 11.91 (11.21-12.59) years, 4031 incident psoriasis events were recorded. There was a positive association between the risk of psoriasis and air pollutant exposure. For every IQR increase in PM2.5, PM10, NO2, and NOx, the hazard ratios (HRs) were 1.41 (95% CI, 1.35-1.46), 1.47 (95% CI, 1.41-1.52), 1.28 (95% CI, 1.23-1.33), and 1.19 (95% CI, 1.14-1.24), respectively. When comparing individuals in the lowest exposure quartile (Q1) with those in the highest exposure quartile (Q4), the multivariate-adjusted HRs were 2.01 (95% CI, 1.83-2.20) for PM2.5, 2.21 (95% CI, 2.02-2.43) for PM10, 1.64 (95% CI, 1.49-1.80) for NO2, and 1.34 (95% CI, 1.22-1.47) for NOx. Moreover, significant interactions between air pollution and genetic predisposition for incident psoriasis were observed. In the subset of 446 637 White individuals, the findings indicated a substantial risk of psoriasis development in participants exposed to the highest quartile of air pollution levels concomitant with high genetic risk compared with those in the lowest quartile of air pollution levels with low genetic risk (PM2.5: HR, 4.11; 95% CI, 3.46-4.90; PM10: HR, 4.29; 95% CI, 3.61-5.08; NO2: HR, 2.95; 95% CI, 2.49-3.50; NOx: HR, 2.44; 95% CI, 2.08-2.87).

Conclusions and relevance: In this prospective cohort study of the association between air pollution and psoriasis, long-term exposure to air pollution was associated with increased psoriasis risk. There was an interaction between air pollution and genetic susceptibility on psoriasis risk.

Figure 1.. Associations of Long-Term Exposure to Fine Particulate Matter With a Diameter Less Than 2.5 µm (PM_2.5), Particulate Matter With a Diameter Less Than 10 µm (PM₁₀), Nitrogen Dioxide (NO₂), and Nitrogen Oxides (NO_x) With the Risk of Psoriasis

A restricted cubic spline regression model with 3 knots (at the 10th, 50th, and 90th percentiles) was used to estimate the dose-response associations between air pollutants and the risk of psoriasis among participants. Hazard ratios (HRs, solid lines) and 95% CIs (shaded areas) were adjusted for age, sex, ethnicity, Townsend Deprivation Index, education, employment, alcohol consumption status, tobacco consumption status, healthy diet score, physical activity, body mass index, kinship to other participants, hypertension, diabetes, and hypercholesterolemia.

Figure 2.. Joint Associations of Long-Term Exposure to Fine Particulate Matter With a Diameter Less Than 2.5 µm (PM_2.5), Particulate Matter With a Diameter Less Than 10 µm (PM₁₀), Nitrogen Dioxide (NO₂), Nitrogen Oxides (NO_x), and Polygenetic Risk Score With the Risk of Incident Psoriasis

Cox regression models adjusted for age, sex, ethnicity, Townsend Deprivation Index, education, employment, alcohol consumption status, tobacco consumption status, healthy diet score, physical activity, body mass index, kinship to other participants, hypertension, diabetes, hypercholesterolemia, genotyping batch, and the first 10 genetic principal components. HR indicates hazard ratio; NA, not applicable; Q1, lowest quartile of exposure to air pollution; and Q4, highest quartile.