Objective:

To systematically dissect sepsis pathogenesis and identify potential therapeutic targets through the integration of cis-pQTL GWAS datasets and multi-omics strategies, emphasizing the role of each strategy in target identification.

Key Findings:

• Identified causal relationships between specific plasma proteins and sepsis risk using MR analysis, contributing to the understanding of sepsis mechanisms.
• Extended previous work by quantitatively assessing the mediating roles of immune cells in the genetic risk of sepsis, highlighting the complexity of immune interactions.
• Utilized large-scale proteomics data to enhance the understanding of sepsis pathogenesis, paving the way for future therapeutic strategies.

Interpretation:

The study provides insights into the biological mechanisms of sepsis and highlights potential plasma protein targets for therapeutic intervention, suggesting pathways for future research.

Limitations:

• Methodological constraints in previous studies, such as small sample sizes and lack of longitudinal data, limited the identification of consistent biomarkers.
• The heterogeneity of sepsis complicates the generalizability of findings across different patient populations, necessitating further validation.

Conclusion:

This research underscores the importance of integrating multi-omics data to identify potential therapeutic targets in sepsis, with GSTP1 emerging as a promising candidate for future therapeutic development.