Evaluating the risk of sepsis attributing to obesity: a two-sample Mendelian randomization study

Background: Sepsis is a reaction to infection with high morbidity and mortality. It has been noted that patients with obesity were more likely to suffer from sepsis. However, the causality remains elucidating, as reverse causality and residual confounding could not be largely mitigated in conventional observational studies.

Objective: To evaluate the risk of sepsis attributed to obesity phenotypes including body mass index (BMI), waist circumstance (WC), and WC adjusted for BMI (WCadjBMI) in a causal way.

Methods: We conducted a two-sample Mendelian randomization (MR) study using large-scale genome-wide association study summary data with sample sizes ranging from 231 353 to 486 484. The inverse-weighted variance (IVW) was conducted as the primary approach. We also used the weighted median and MR-Egger for causal inference. A sensitivity analysis was conducted to evaluate the reliability of the MR estimates.

Results: IVW detected that genetic liability for increased BMI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.20-1.63, P = 1.52 × 10-5] and WC (OR = 1.02, 95% CI = 1.01-1.03, P = 4.28 × 10-3) predicted a higher risk of sepsis. No evidence was observed for a causal effect of WCadjBMI on sepsis risk (OR = 1.01, 95% CI = 1.00-1.02, P = 0.08). Sensitivity analysis did not identify any bias in the MR results.

Conclusion: This MR study showed that obesity contributed to an increased risk of sepsis, indicating that obesity management might be beneficial for reducing sepsis risk. Key messages What is already known on this topic-Observational studies have reported the association between obesity and sepsis, but the causality has not been determined. What this study adds-This Mendelian randomization study demonstrated that obesity-related phenotypes, including body mass index and Waist circumstance, causally increased the risk of sepsis. How this study might affect research, practice, or policy-The findings of our study might have an implication for clinicians that obesity management might be a promised strategy for reducing the risk of sepsis.