Exploring the Causal Relationship Between Circulating miRNAs and Sepsis Through Mendelian Randomization Analysis

BackgroundMicroRNAs (miRNAs) play a crucial role in the pathophysiology of sepsis, with aberrant expression documented in peripheral blood samples from sepsis patients. This study aims to investigate the causal relationship between circulating miRNAs and sepsis using Mendelian Randomization (MR) approaches.MethodsWe utilized miRNA expression quantitative trait loci (eQTL) data and genome-wide association study (GWAS) data on sepsis. MR analysis was conducted using Inverse Variance Weighted (IVW) and MR-Egger regression methods to identify miRNAs significantly associated with sepsis risk. Potential targets and related pathways of these miRNAs were also analyzed.ResultsIVW and MR-Egger regression analyses revealed that three circulating miRNAs (hsa-miR-125a-5p, hsa-miR-494-3p, and hsa-miR-885-5p) exhibited significant associations with reduced sepsis risk, indicating protective effects. Conversely, hsa-miR-196b-5p, hsa-miR-27b-3p, and hsa-miR-598-3p were linked to increased sepsis risk. The association between hsa-miR-27b-3p and increased sepsis risk was further validated in an independent cohort. Target identification and enrichment analysis indicated that the targets of these miRNAs are closely related to biological processes such as bacterial infection, apoptosis, and the FoxO signaling pathway.ConclusionOur study provides novel insights into the causal relationships between circulating miRNAs and sepsis through MR analysis, offering new perspectives for early prevention and treatment strategies for sepsis. These findings provide a foundation for further investigation into the potential application of miRNAs in the diagnosis and treatment of sepsis.