Exploring the Potential Causal Relationship between Protein Ratio and Atopic Dermatitis Using a Two-Sample Mendelian Randomization Approach

Background: Recently, a series of observational studies have uncovered potential associations between protein ratios and atopic dermatitis. Nevertheless, the specific mechanisms underlying this physiological process remain shrouded in mystery and await further elucidation. In light of this current situation, we have adopted the innovative strategy of Mendelian Randomization (MR) as a research tool, aiming to delve deeply into and validate the potential causal relationship between protein ratios and atopic dermatitis. This endeavor seeks to provide novel insights and evidence for unraveling the pathophysiological mechanisms involved. Methods: Using MiBioGen resources, we compiled genetic variation data on protein ratios from a large GWAS dataset for a two-sample MR study on atopic dermatitis. Data from FinnGen's GWAS database (2,385 cases, 209,651 controls) were analyzed with multiple MR methods (IVW, MR-Egger, weighted median/mode, simple mode) to explore causality. Cochran's Q and MR Egger intercept tests assessed heterogeneity and pleiotropy, respectively, ensuring accuracy. Our goal is to uncover the causal link between protein ratios and atopic dermatitis, informing future mechanism studies. Results: In this meticulously planned study, we comprehensively employed Mendelian randomization analysis techniques to delve deeply into the complex and subtle connections between protein ratios and atopic dermatitis. The findings unveiled several compelling statistically significant associations, which directly pointed to the intimate relationship between specific protein ratio changes and the risk of developing atopic dermatitis. Specifically, we identified a series of protein ratios, including CLIP2/PDLIM7, CNDP1/F9, ANXA3/MSRA, among others, whose elevations significantly elevate the risk of atopic dermatitis, seemingly playing a role in promoting disease onset. Conversely, increases in other protein ratios, such as ENG/TNFRSF10C, CD300LG/TNFRSF1B, and FIS1/NCK2, exhibited inhibitory effects on the risk of atopic dermatitis, suggesting a potential protective role for these protein ratios. These discoveries have significantly enriched our understanding of the crucial role protein ratios play in maintaining skin health and have laid a solid genetic foundation for exploring novel avenues for atopic dermatitis prevention and treatment. In the future, these research outcomes hold promise to be translated into effective intervention strategies, alleviating the burden on patients with atopic dermatitis and enhancing their quality of life. Conclusion: The protein ratios identified through Mendelian randomization studies as being associated with atopic dermatitis offer precise clinical targets for the treatment of this condition. Looking ahead, an enhanced comprehension of the causal relationship between these protein ratios and atopic dermatitis will pave the way for further investigations into their therapeutic potential, ultimately advancing the management of this disease.