Genetic Insights Into Skin Diseases and Depression: Evidence From East Asian Mendelian Randomization Analysis.

Background: This Mendelian randomization (MR) study systematically examines the causal links between skin disorders and depression in individuals of East Asian descent. Methods: MR analysis employed summary-level genome-wide association study (GWAS) data from East Asian populations. Exposures included six skin diseases: atopic dermatitis (AD) (n = 168,103), urticaria (n = 172,083), vitiligo (n = 13,327), systemic lupus erythematosus (SLE) (n = 51,009), psoriasis (n = 69,688) and acne (n = 2062). Depression was assessed using major depressive disorder (MDD) data from the Psychiatric Genomics Consortium (n = 194,548). The primary analytical methods were the inverse variance weighting (IVW) and Wald Ratio. Sensitivity analyses were conducted to detect heterogeneity and pleiotropy, incorporating Steiger tests to mitigate reverse causation. Results: In East Asian ancestries, a significant causal relationship was identified between urticaria and an increased risk of MDD (odds ratio [OR] = 1.220, 95% CI 1.022-1.457, p = 0.028). No significant causal link was found between psoriasis and MDD. Both findings are in stark contrast to those from previous MR studies of European ancestries. No significant causal associations were observed between AD, vitiligo, SLE, acne and MDD, consistent with previous MR studies in European populations. Sensitivity analyses revealed no significant evidence of heterogeneity or pleiotropy, supporting the robustness of the causal evidence. Conclusions: This study identifies a significant positive causal relationship between urticaria and MDD risk and no significant association between psoriasis and MDD in East Asian populations, contrasting with previous European findings. Results for other skin diseases align with previous studies. These findings highlight the need for ancestry-specific research to inform personalized prevention and intervention strategies.