Identifying potential drug targets for postoperative abdominal wall hernia using Mendelian randomization: a...

Area of Science:

• Genetics and Pharmacology
• Surgical Complications Research

Background:

• Postoperative abdominal wall hernia is a significant surgical complication.
• Identifying effective drug targets is crucial for preventing and treating this condition.

Purpose of the Study:

• To identify novel druggable targets for postoperative abdominal wall hernia using a multi-omics approach.
• To validate cathepsin S (CTSS) as a potential therapeutic target.

Main Methods:

• Mendelian Randomization (MR) integrated druggable gene, cis-protein quantitative trait loci (pQTL), and cis-expression quantitative trait loci (eQTL) data.
• Colocalization analysis, Summary Data-Based Mendelian Randomization (SMR), drug side effect assessment, and molecular docking were performed.
• FinnGen R11 population data was utilized for the analysis.

Main Results:

• Mendelian Randomization analysis identified cathepsin S (CTSS) as a druggable gene positively associated with postoperative abdominal wall hernia (FDR < 0.05).
• Colocalization analysis confirmed the association, and a key variant (rs41305070) was identified.
• Molecular docking and side effect evaluations supported CTSS as a viable drug target.

Conclusions:

• Elevated CTSS levels are linked to an increased risk of postoperative abdominal wall hernia.
• CTSS represents a promising therapeutic target for the prevention and treatment of postoperative abdominal wall hernia.