Stensrud Vilde Hatlevoll, Rogne Tormod, Flatby Helene Marie, Mohus Randi Marie, Gustad Lise Tuset, Nilsen Tom Ivar Lund
Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
BMC Infect Dis. 2025 May 23;25(1):739. doi: 10.1186/s12879-025-11130-y.
Educational attainment is inversely related to sepsis risk, but the causal nature is still unclear. We therefore conducted the first Mendelian randomization (MR) study of genetically predicted educational attainment on sepsis that also uses a within-family genetic instrument for education. To further explore possible mechanistic pathways that can inform strategies to reduce sepsis risk, we examined the mediating effects of factors that are modifiable or can be prevented.
The association between genetically predicted educational attainment and sepsis was estimated using summary-level data from recent genome-wide association studies. Possible bias due to population stratification, dynastic effects, and assortative mating in the genetic instrument for education was evaluated using summary-level data from a within-sibship genome-wide association study. We used inverse variance weighted MR analysis to estimate the effect of one standard deviation increase in years of education on sepsis risk. The robustness of the findings was assessed in sensitivity analyses, applying weighted median, weighted mode, and MR Egger regression. Finally, we applied multivariable MR analyses to estimate the mediating effects of smoking initiation, alcohol consumption, body mass index, high-density lipoprotein (HDL)-cholesterol, systolic blood pressure and type 2 diabetes.
For each standard deviation increase in genetically predicted educational attainment (3.4 years), the odds ratio (OR) for sepsis was 0.72 (95% confidence interval (CI) 0.66 to 0.78). The results of the analysis using the within-sibship genetic instrument and other sensitivity analyses were in line with this finding: within-sibship OR 0.88 (95% CI 0.64 to 1.18), weighted median OR 0.70 (95% CI 0.62 to 0.80), weighted mode OR 0.70 (95% CI 0.43 to 1.13), and MR Egger OR 0.65 (95% CI 0.50 to 0.85). The mediation analysis showed that 56% of the effect of educational attainment on sepsis risk can be explained by modifiable or preventable factors.
Higher educational attainment is strongly associated with a reduced risk of sepsis, pointing to important socioeconomic differences in this disease. The results also suggest that interventions targeting modifiable or preventable factors could contribute to reducing the socioeconomic differences in sepsis risk.
受教育程度与脓毒症风险呈负相关，但其因果性质仍不明确。因此，我们开展了第一项关于基因预测的受教育程度对脓毒症影响的孟德尔随机化（MR）研究，该研究还使用了家庭内部的基因工具来衡量教育程度。为了进一步探索可能的机制途径，以便为降低脓毒症风险的策略提供依据，我们研究了可改变或可预防因素的中介作用。
利用近期全基因组关联研究的汇总数据，估计基因预测的受教育程度与脓毒症之间的关联。使用同胞基因组范围内关联研究的汇总数据，评估教育基因工具中由于人群分层、王朝效应和选型交配可能导致的偏差。我们使用逆方差加权MR分析来估计教育年限增加一个标准差对脓毒症风险的影响。在敏感性分析中，应用加权中位数、加权众数和MR Egger回归评估研究结果的稳健性。最后，我们应用多变量MR分析来估计吸烟起始、饮酒、体重指数、高密度脂蛋白（HDL）胆固醇、收缩压和2型糖尿病的中介作用。
基因预测的受教育程度每增加一个标准差（3.4年），脓毒症的比值比（OR）为0.72（95%置信区间（CI）0.66至0.78）。使用同胞基因工具的分析结果和其他敏感性分析结果与此发现一致：同胞内OR为0.88（95%CI 0.64至1.18），加权中位数OR为0.70（95%CI 0.62至0.80），加权众数OR为0.70（95%CI从0.43至1.13），MR Egger OR为0.65（95%CI 0.50至0.85）。中介分析表明，受教育程度对脓毒症风险的影响中有56%可由可改变或可预防的因素解释。
受教育程度较高与脓毒症风险降低密切相关，表明该疾病存在重要的社会经济差异。研究结果还表明，针对可改变或可预防因素的干预措施可能有助于减少脓毒症风险方面的社会经济差异。
