Identifying novel risk targets in inflammatory skin diseases by comprehensive proteome-wide Mendelian randomization...

Area of Science:

• Genetics and immunology
• Proteomics and bioinformatics

Background:

• Early diagnosis and treatment of inflammatory skin diseases remain challenging despite advances in targeted therapies.
• Identifying causal links between circulating proteins and conditions like acne, atopic dermatitis, and psoriasis is crucial.

Purpose of the Study:

• To identify circulating proteins causally associated with inflammatory skin diseases using a Mendelian randomization (MR) framework.
• To explore potential therapeutic targets for inflammatory skin diseases based on identified protein associations.

Main Methods:

• Large-scale Mendelian randomization (MR) analysis of thousands of plasma proteins and common inflammatory skin diseases.
• Utilized Steiger filtering, transcriptome-wide association studies, and Bayesian colocalization for validation.
• Explored protein-protein interaction networks, pathway enrichment, and drug target evaluation.

Main Results:

• Identified over 100 circulating proteins potentially involved in inflammatory skin diseases.
• Highlighted RARRES2, SERPINC1, GALK1, and ECM1 as Tier 1 targets for atopic dermatitis.
• Identified RARRES2, PPID, and IL1RL1 as potential targets for acne, rosacea, and urticaria.

Conclusions:

• The MR analysis revealed numerous plasma proteins associated with inflammatory skin diseases, offering insights into protein-mediated mechanisms.
• Identified promising therapeutic targets, including RARRES2 and IL1RL1, for future interventions.
• Findings suggest new diagnostic and therapeutic avenues for inflammatory skin diseases, requiring further clinical validation.