Psychiatric morbidity, genetic susceptibility and the risk of vitiligo

Abstract Background Vitiligo is a complex autoimmune skin disorder influenced by genetic susceptibility and environmental factors. Psychiatric morbidity has been proposed as a potential antecedent or correlate of vitiligo, but its prospective association with incident vitiligo remains unclear. Objectives To investigate the prospective association between psychiatric morbidity and vitiligo and determine the extent to which this association is modified by genetic susceptibility, quantified by polygenic risk scores (PRS). Methods This study included 379,589 UK Biobank participants. Psychiatric morbidity and vitiligo were ascertained using ICD‐10 codes. A vitiligo‐specific PRS was analysed as elevated versus non‐elevated genetic risk. Cox proportional hazards models were employed to evaluate associations, followed by interaction and exploratory pathway analyses. Results During a median follow‐up of 13.6 years, anxiety (HR 1.78, 95% CI 1.23–2.56) and depression (HR 1.46, 95% CI 1.03–2.06) were associated with incident vitiligo in the fully adjusted model. Elevated PRS was associated with higher vitiligo risk (HR 1.48, 95% CI 1.17–1.88). Stratified analyses revealed heterogeneous effects of psychiatric morbidity across genetic backgrounds. Participants with both psychiatric morbidity and elevated PRS had the highest point estimate (HR 2.28, 95% CI 1.06–4.88). Exploratory pathway analyses suggested lymphocyte percentage as a possible immune‐related marker. Conclusion Hospital‐recorded psychiatric morbidity and elevated genetic susceptibility were prospectively associated with incident vitiligo. These observational findings support consideration of mental health in holistic vitiligo care, while causal mechanisms require independent validation.