• Jing Hu, Quan Gan, Dong Zhou, Xing Xia, Wei Xiang, Rong Xiao, Jing Tang, and Jie Li.
• Department of Medical Intensive Care Unit, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430070, China.
• Postgrad Med J. 2023 Nov 20; 99 (1178): 126612711266-1271.

BackgroundSepsis 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.ObjectiveTo 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.MethodsWe 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.ResultsIVW 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.ConclusionThis 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.© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal.

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