Phenome-wide Mendelian randomization analysis reveals new risk factors for 4 inflammatory skin diseases

In dermatology, the understanding of the causal relationships between risk factors and inflammatory skin diseases has been an area of continuous research. Although many earlier studies have confirmed the causal relationships between some risk factors and 4 inflammatory skin diseases (acne vulgaris, atopic dermatitis [AD], psoriasis, and vitiligo). However, many new exposure factors still need to be discovered and confirmed by us which could significantly enhance our understanding of disease etiology and inform more effective prevention and treatment strategies. To bridge this knowledge gap, we conducted a phenome-wide Mendelian randomization analysis to explore the causal relationships between 3617 traits and 4 inflammatory skin diseases (acne vulgaris, AD, psoriasis, and vitiligo). These 3617 traits encompassed a broad spectrum, including: other diseases, dietary intake, anthropometric measures, immune and inflammatory factors, fatty acid and lipoprotein metabolism, lifestyle and behavior, metabolomics and proteomics. We employed Mendelian randomization analysis primarily based on 2 methods and conducted pleiotropy and heterogeneity checks to enhance the robustness of the results. Additionally, data from the FinnGen cohort was used for validation further improving the robustness of the results. The results of the Mendelian randomization analysis and subsequent verification indicate that 3 exposures are significantly associated with acne, including galanin and galanin message-associated peptide prepropeptide, among others. Furthermore, 18 exposures have been identified as suggestively associated, such as stearoylcarnitine and related compounds. In the context of AD, there are 8 significant exposures, including asthma, eosinophil cell count and so forth, and 59 suggestive exposures, such as sum eosinophil basophil counts, inflammatory bowel disease, et cetera. In the context of psoriasis, the analysis identified 16 significant exposures, including Trefoil factor 3, among others. Furthermore, 31 exposures were identified as suggestive, such as the sum of neutrophil and eosinophil counts, and interleukin 16. Finally, in the case of vitiligo, the analysis revealed 12 significant exposures, including childhood sunburn occasions, and 11 suggestive exposures, such as the percentage of eosinophils. This study provides new insights into exploring the causal relationship between new risk factors and 4 inflammatory skin diseases as well as the prevention and treatment of these 4 inflammatory skin diseases.