血浆肿瘤坏死因子相关凋亡诱导配体水平对脓毒症28天死亡的因果关系:一项两样本孟德尔随机化研究OA
The causal relationship between plasma tumor necrosis factor-related apoptosis-inducing ligand level and 28-day death from sepsis:a two-sample Mendelian randomization study
目的 应用两样本孟德尔随机化(MR)法分析血浆肿瘤坏死因子相关凋亡诱导配体(TRAIL)水平与脓毒症28d死亡之间的因果关系.方法 以已发表的全基因组关联分析为数据来源,从中筛选与脓毒症28d死亡显著相关的单核苷酸多态性(SNP)作为工具变量.采用逆方差加权(IVW)法、MR-Egger分析法、加权中位数估计法和加权模式法共4种方法进行两样本MR分析,评估血浆TRAIL水平与脓毒症28 d死亡率之间的因果关系.应用"留一"法进行敏感性分析,应用Cochran Q检验进行异质性检测,应用MR-Egger截距检验分析结果的水平多效性.结果 最终选取10个强工具变量进行两样本MR分析.IVW法分析结果显示,血浆TRAIL水平与脓毒症28 d死亡率之间存在因果关系[OR=1.186,95％CI(1.005～1.340),P=0.044];其他三种分析方法结果均支持血浆TRAIL水平与脓毒症28 d死亡率之间存在因果关系.敏感性分析提示MR分析结果稳健,异质性分析结果提示SNP之间不存在异质性,多效性分析结果提示工具变量不存在水平多效性(均P＞0.05),漏斗图提示结果无偏倚.结论 TRAIL与脓毒症28 d死亡率之间存在因果关系,血浆TRAIL水平升高可增加脓毒症28 d死亡的风险.
Objective To investigate the causal relationship between plasma tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)level and 28-day death from sepsis by two-sample Mendelian randomization.Methods Published genome-wide association studies were the data sources,from which single nucleotide polymorphisms significantly associated with 28-day death from sepsis were screened out to serve as instrumental variables.In order to evaluate the causal relationship between plasma TRAIL level and 28-day death from sepsis,4 methods,including inverse variance weighted(IVW)method,MR-Egger analysis method,weighted median estimator method,and weighted mode method,were used to perform the two-sample MR analysis.Sensitivity analysis was performed using the leave-one-out method,heterogeneity test using the Cochran's Q test,and the horizontal pleiotropy of the results using the MR-Egger intercepe test.Results A total of 10 strong instrumental variables were selected for the two-sample MR analysis.The results of IVW analysis showed that there was a causal relationship between plasma TRAIL level and 28-day death from sepsis[OR=1.186,95％CI(1.004～1.339),P=0.044],which was supported by the other three analyses.Sensitivity analysis results showed that the MR analysis results were steady,heterogeneity test results showed that there was no heterogeneity among SNPs,and the pleiotropy analysis results showed that there was no horizontal pleiotropy in the instrumental variables(all P＞0.05).The funnel plot showed that the results were unbiased.Conclusion There is a causal relationship between TRAIL and 28-day mortality from sepsis,and an elevated plasma TRAIL level increases the risk of 28-day death from sepsis.
孙慧颖;刘雪燕;李梦瑶;许智坤
暨南大学第二临床医学院,广东省深圳市 518020广东省深圳市人民医院重症医学科,深圳市 518020
临床医学
肿瘤坏死因子相关凋亡诱导配体脓毒症孟德尔随机化因果关系单核苷酸多态性死亡
Tumor necrosis factor-related apoptosis-inducing ligandsepsisMendelian randomizationSingle nucleotide polymorphismsDeath
《内科》 2024 (003)
296-301 / 6
广东省深圳市科技创新委员会可持续发展科技专项(专2023N044)
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