Abstract
BACKGROUND: Atopic dermatitis (AD) arises from complex gene-environmental interactions, and urban exposures are increasingly linked to its pathogenesis. OBJECTIVE: To investigate the independent and interactive effects of urbanization-related exposures (air pollution, noise, traffic, green space) on AD incidence stratified by genetic susceptibility. METHODS: Within the prospective UK Biobank cohort (n = 306,837), genetic risk was categorized by polygenic risk score. Associations and dose-response relationships were assessed using Cox and restricted cubic spline models. RESULTS: Moderate and high air pollution mixtures were significantly associated with a higher AD risk, showing dose-dependent relationships. Higher green space coverage was associated with lower AD risk, particularly in the high genetic risk group (hazard ratio: 0.609, 95% confidence interval: 0.479-0.774). Noise was linked to an elevated AD risk exclusively in high genetic susceptibility, while urban residence and traffic load were associated with increased AD risk irrespective of genetic background. In a mutually adjusted multivariable model, the effects of traffic load and noise were attenuated. LIMITATIONS: Restricted ancestry, indoor pollutants, and residential mobility. CONCLUSION: Urban exposures show dose-dependent associations with AD risk. The assessment of urbanization exposure, in addition to genetic profiling, may represent a practical approach for population-level AD risk assessment and prevention.