孟德尔随机化
败血症
医学
优势比
混淆
免疫学
全基因组关联研究
观察研究
生物信息学
内科学
遗传学
生物
基因型
单核苷酸多态性
基因
遗传变异
作者
Feng Zhi,Jian Ma,Dandan Ji,Jie Bao,Qianqian Li
标识
DOI:10.3389/fimmu.2024.1336586
摘要
Sepsis represents a critical medical condition that arises due to an imbalanced host reaction to infection. Central to its pathophysiology are cytokines. However, observational investigations that explore the interrelationships between circulating cytokines and susceptibility to sepsis frequently encounter challenges pertaining to confounding variables and reverse causality.To elucidate the potential causal impact of cytokines on the risk of sepsis, we conducted two-sample Mendelian randomization (MR) analyses. Genetic instruments tied to circulating cytokine concentrations were sourced from genome-wide association studies encompassing 8,293 Finnish participants. We then evaluated their links with sepsis and related outcomes using summary-level data acquired from the UK Biobank, a vast multicenter cohort study involving over 500,000 European participants. Specifically, our data spanned 11,643 sepsis cases and 474,841 controls, with subsets including specific age groups, 28-day mortality, and ICU-related outcomes.MR insights intimated that reduced genetically-predicted interleukin-10 (IL-10) levels causally correlated with a heightened sepsis risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.52-0.90, P=0.006). An inverse relationship emerged between monocyte chemoattractant protein-1 (MCP-1) and sepsis-induced mortality. Conversely, elevated macrophage inflammatory protein 1 beta (MIP1B) concentrations were positively linked with both sepsis incidence and associated mortality. These revelations underscore the causal impact of certain circulating cytokines on sepsis susceptibility and its prognosis, hinting at the therapeutic potential of modulating these cytokine levels. Additional research is essential to corroborate these connections.
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