阿司匹林与细菌性肺炎风险的因果关系:来自欧洲人群的全基因组关联研究大数据分析  

Causal relationship between aspirin and the risk of bacterial pneumonia:big data analysis of the genome-wide association study from European populations

作　　者：李泽荣 樊斌 邱放 杨明 乔文梅 LI Zerong;FAN Bin;QIU Fang;YANG Ming;QIAO Wenmei(Department of Pharmacy,Shenzhen University First Affiliated Hospital,Shenzhen Second People's Hospital,Shenzhen 518035,Guangdong Province,China;Department of Pharmacy,Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen Third People's Hospital,Shenzhen 518112,Guangdong Province,China)

机构地区：[1]深圳市第二人民医院/深圳大学第一附属医院药学部,广东深圳518035 [2]深圳市第三人民医院/南方科技大学第二附属医院药学部,广东深圳518112

出　　处：《药学前沿》2025年第4期609-616,共8页China Pharmacist

基　　金：国家自然科学基金(82200300);广东省医院药学研究基金(复星基金)(2024A02018);广东省医院药学儿科呼吸用药专项研究基金(2024EKHX07);广东省药学会科学研究基金-ERAS患者管理体系构建专项(2024ERAS16);广东省临床用药研究基金(临床治疗精准用药专项)(2023JZ12)。

摘　　要：目的通过两样本孟德尔随机化(MR)方法来探索阿司匹林治疗与细菌性肺炎发病风险之间的遗传因果关系。方法从公开可用的欧洲人群全基因组关联研究数据库中分别获取与阿司匹林治疗及细菌性肺炎密切相关的遗传数据集,通过8种方法(IVW、MR egger、Weighted median、Simple mode、Weighted mode、MR-RAPS、cML-MA、ConMix)进行MR分析。MR分析结果的异质性、敏感性和多效性分别通过Cochran's Q检验、MREgger截距检验、MR-PRESSO法和留一法进行评估。C反应蛋白、缺血性心脏病、体重指数、低密度脂蛋白胆固醇、血压/高血压病和糖尿病作为混杂因素被纳入分析。结果M R分析的IVW结果表明,遗传预测的阿司匹林治疗与细菌性肺炎风险之间存在负向因果关系[OR=0.073,95%CI(0.021,0.251),P=3.35×10^(-5)]。在阿司匹林治疗与细菌性肺炎风险的MR分析中,Cochran's Q检验提示该分析结果无异质性;MR-PRESSO分析和MR-Egger截距检验提示结果无水平多效性;leave-one-out法提示结果稳健性良好。剔除混杂因素后再次分析得出的因果关联仍然支持该结果。结论该MR研究支持阿司匹林治疗对细菌性肺炎风险的保护作用的结论,然而,未来将需要更多的基础和临床研究来进一步验证。Objective To explore the genetic causal relationship between aspirin treatment and the risk of bacterial pneumonia through two sample Mendelian randomization(MR)method.Methods Genetic datasets closely related to aspirin treatment and bacterial pneumonia were obtained from publicly available European genome-wide association study databases,and MR analysis was conducted using eight MR analysis methods(IVW,MR egger,Weighted median,Simple mode,Weighted mode,MR-RAPS,cML-MA,ConMix).The heterogeneity,sensitivity,and pleiotropy of MR analysis results were evaluated using Cochran's Q test,MR Egger intercept test,MR-PRESSO method and leave-one-out method,respectively.C-reactive protein,ischemic heart disease,body mass index,low density lipoprotein cholesterol,blood pressure/hypertension,and diabetes mellitus were included in the analysis as confounders.Results The IVW results of MR analysis showed that there was a negative causal relationship between genetically predicted aspirin treatment and bacterial pneumonia[OR=0.073,95%CI(0.021,0.251),P=3.35×10^(-5)].After analyzing the relationship between aspirin treatment and the risk of bacterial pneumonia using MR methods,Cochran's Q test showed no heterogeneity in the analysis results,the MR-PRESSO analysis and MR-Egger intercept test indicated no horizontal pleiotropy in the results,the leave-one-out method indicated good robustness of the results.The causal associations derived from the reanalysis after excluding the confounders still support this result.Conclusion This MR analysis supports that aspirin has protective effects against bacterial pneumonia.However,more basic and clinical research will be needed to support the findings in the future.

关 键 词：阿司匹林 细菌性肺炎 孟德尔随机化 因果推断 

分 类 号：R979.9[医药卫生—药品]