Evaluating the Causal Effects of Circulating Proteome on the Risk of Sepsis and Related Outcomes

The current investigation deployed Mendelian randomization (MR) to elucidate the causal relationship between circulating proteins and sepsis. A rigorous two-sample MR analysis evaluated the effect of plasma proteins on the sepsis susceptibility. To affirm the integrity of MR findings, a suite of supplementary analyses, including Bayesian colocalization, Steiger filtering, the assessment of protein-altering polymorphisms, and the correlation between expression quantitative trait loci and protein quantitative trait loci (pQTLs), was employed. The study further integrated the examination of protein-protein interactions and pathway enrichment, along with the identification of pharmacologically actionable targets, to advance our comprehension and outline potential sepsis therapies. Subsequent analyses leveraging