Association of Modifiable Lifestyle and Metabolic Factors With the Risk of Developing Sepsis: 2-Sample Mendelian Randomized Study

作者：Haifeng Lv, Jing Liu, Yelin Cao, Weina Fan, Guojie Shen, Feifei Wang, Qingqing Ye, Xiaoliang Wu, Kaijin Xu · 发表于：Interactive Journal of Medical Research · 年份：2025 · DOI：10.2196/72244 · 研究领域：Sepsis Diagnosis and Treatment、Immune Response and Inflammation、Inflammation biomarkers and pathways

Background: Sepsis is a life-threatening condition characterized by organ dysfunction resulting from dysregulated host response to infections. Approximately 48.9 million people worldwide are diagnosed with sepsis annually, leading to 11 million deaths and representing 19.7% of all global deaths. No specific, effective treatments for sepsis, which has a poor prognosis, are available. Objective: The study aimed to systematically explore the association between genetically predicted modifiable risk factors and sepsis. Methods: Univariable 2-sample Mendelian randomization (MR) analysis was performed to explore the association between 30 modifiable risk factors (12 lifestyle, 3 educational and psychological, and 15 metabolic factors) and sepsis. Heterogeneity was evaluated using the Cochran Q analysis. Sensitivity analyses were conducted using the MR-Egger regression intercept tests and leave-one-out analyses. Additionally, multivariable MR analyses were performed to adjust for genetic associations between the instruments and obesity. Results: Genetically predicted smoking (odds ratio [OR] 1.20, 95% CI 1.06-1.36; P=.005), a higher number of cigarettes smoked daily (OR 1.70, 95% CI 1.29-2.23; P<.001), a higher overall health rating (OR 2.19, 95% CI 1.61-2.98; P<.001), BMI (OR 1.50, 95% CI 1.38-1.63; P<.001), waist circumference (OR 1.70, 95% CI 1.53-1.89; P<.001), whole body fat mass (OR 1.50, 95% CI 1.37-1.64; P<.001), trunk fat mass (OR 1.48, 95% CI 1.36-1.62; P<.001), arm fat ma...