Integrative Genetic Perspectives: Decoding the Relationship Between Micronutrients, Inflammatory Cytokines, and Inflammatory Skin Diseases

ABSTRACT This study employed Mendelian randomization (MR) to investigate the potential causal relationships between micronutrients, inflammatory proteins, and inflammatory skin diseases. Two‐sample MR and multivariate MR (MVMR) were conducted to assess the causal effects of 15 micronutrients on 13 inflammatory skin diseases. Mediation MR analysis was further utilized to evaluate the mediating roles of 91 inflammatory cytokines. The inverse variance weighted (IVW) method served as the primary analytical approach, complemented by comprehensive sensitivity analyses. The MR analysis revealed a significant causal association where genetically predicted higher Vitamin B6 levels increased the risk of Hidradenitis Suppurativa (HS) (FDR < 0.05). Suggestive associations ( p < 0.05, FDR ≥ 0.05) were also observed: Folate was associated with a reduced risk of folliculitis; Potassium with a reduced risk of pityriasis rosea; Vitamin B12 with a reduced risk of urticaria; Carotene with an increased risk of rosacea; Vitamin C with a decreased risk of rosacea; and Calcium with an increased risk of HS. Crucially, MVMR indicated that the effects on rosacea and HS were not independent, suggesting synergistic interactions among nutrients. Mediation analysis further demonstrated that folate may partially reduce the risk of folliculitis by lowering the levels of Caspase‐8. The findings were robust across sensitivity analyses. In conclusion, this study provides genetic evidence for potential causal effects of specific micronutrients on inflammatory skin diseases, revealing possible synergistic interactions and mediation via inflammatory proteins. These insights may inform future nutritional interventions and disease management strategies.