Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
Neurological Intensive Care Unit, Department of Neurosurgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Sci Rep. 2024 Mar 8;14(1):5718. doi: 10.1038/s41598-024-56467-7.
Cardio-metabolic traits have been reported to be associated with the development of sepsis. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability, or are confounded by environmental factors. We performed three analyses to explore the relationships between cardio-metabolic traits and sepsis. Mendelian randomization (MR) study to evaluate the causal effects of multiple cardio-metabolic traits on sepsis. Global genetic correlation analysis to explore the correlations between cardio-metabolic traits and sepsis. Local genetic correlation (GC) analysis to explore shared genetic heritability between cardio-metabolic traits and sepsis. Some loci were further examined for related genes responsible for the causal relationships. Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies with sample sizes between 200,000 to 750,000. In MR, we found causality between BMI and sepsis (OR: 1.53 [1.4-1.67]; p < 0.001). Body mass index (BMI), which is confirmed by sensitivity analyses and multivariable MR adjusting for confounding factors. Global GC analysis showed a significant correlation between BMI and sepsis (r = 0.55, p < 0.001). More cardio-metabolic traits were identified to be correlated to the sepsis onset such as CRP (rg = 0.37, p = 0.035), type 2 diabetes (r = 0.33, p < 0.001), HDL (r = - 0.41, p < 0.001), and coronary artery disease (r = 0.43, p < 0.001). Local GC revealed some shared genetic loci responsible for the causality. The top locus 1126 was located at chromosome 7 and comprised genes HIBADH, JAZF1, and CREB5. The present study provides evidence for an independent causal effect of BMI on sepsis. Further detailed analysis of the shared genetic heritability between cardio-metabolic traits and sepsis provides the opportunity to improve the preventive strategies for sepsis.
代谢性心血管特征与脓毒症的发生有关。然而，目前尚不清楚这些合并症是否反映了因果关系、共同的遗传遗传性，还是受环境因素的影响。我们进行了三项分析，以探讨代谢性心血管特征与脓毒症之间的关系。孟德尔随机化 (MR) 研究评估了多种代谢性心血管特征对脓毒症的因果影响。全基因组遗传相关性分析探索了代谢性心血管特征与脓毒症之间的相关性。局部遗传相关性 (GC) 分析探讨了代谢性心血管特征与脓毒症之间的共同遗传遗传性。进一步检查了一些与因果关系相关的基因。遗传关联来自 UK Biobank 数据或已发表的大型全基因组关联研究，样本量在 200,000 到 750,000 之间。在 MR 中，我们发现 BMI 与脓毒症之间存在因果关系（OR：1.53 [1.4-1.67]；p < 0.001）。BMI 通过敏感性分析和多变量 MR 调整混杂因素得到确认。全基因组 GC 分析显示 BMI 与脓毒症之间存在显著相关性（r = 0.55，p < 0.001）。更多的代谢性心血管特征与脓毒症发病相关，如 CRP（rg = 0.37，p = 0.035）、2 型糖尿病（r = 0.33，p < 0.001）、高密度脂蛋白（r = -0.41，p < 0.001）和冠心病（r = 0.43，p < 0.001）。局部 GC 揭示了一些负责因果关系的共同遗传位点。位于第 7 号染色体的 1126 号位点包含 HIBADH、JAZF1 和 CREB5 基因。本研究为 BMI 对脓毒症的独立因果作用提供了证据。进一步详细分析代谢性心血管特征与脓毒症之间的共同遗传遗传性为改善脓毒症的预防策略提供了机会。
