How does OA affect sepsis? An observational study and Mendelian randomization mediation analysis

To investigate the causal relationships among osteoarthritis (OA), sepsis, and potential mediators, which include immune cell phenotypes, metabolic, and inflammation.

Firstly, the observational study extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure was OA and the control group was patients without any diagnosis of OA. The outcome was a diagnosis of sepsis in the ICU. Secondly, we analyzed summary data from genome-wide association studies on OA, 731 immune cell phenotypes, 1400 plasma metabolites, 91 inflammation factors, and sepsis (diagnosis and 28-day survival), with GWAS datasets including up to ∼30 million SNPs for OA phenotypes and ∼12 million SNPs for sepsis-related outcomes. Bidirectional Mendelian Randomization (MR) analysis was conducted to explore the causal links between OA and sepsis.

In observational study, the MIMIC-IV study did not observe a significant association between any OA and sepsis (Odds Ratio (OR) = 1.04, 95% CI: 0.87-1.24). Similarly, lower limb OA showed no correlation with sepsis (OR = 1.21, 95% CI: 0.82-1.77). However, a causal effect of hip osteoarthritis on the risk of developing sepsis was identified (OR: 1.09, 95% CI: 1.01-1.18, P = 0.024). Additionally, we found that sphingomyelin levels and X-24585 levels act as mediators in the causal relationship between hip OA and sepsis, with mediation proportions of 12.4% and 14.2%, respectively.

No association between OA and sepsis diagnosis was observed in this cross-sectional study, possibly due to confounding. However, with the MR analysis in GWAS data, hip OA emerged as a potential risk factor for sepsis, with metabolic factor likely acting as mediator. Further mechanisms remain unclear.