免疫细胞在心肌炎中的因果作用:两样本与多变量孟德尔随机化研究  

Immune cells and myocarditis:a two-sample and multivariate Mendelian randomization study

作　　者：薛思杨 姜红菊[1] XUE Si-yang;JIANG Hong-ju(The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Department of Cardiology,Jinan,Shandong 250001,China)

机构地区：[1]山东中医药大学第二附属医院心血管病科,山东济南250001

出　　处：《现代预防医学》2024年第10期1748-1753,共6页Modern Preventive Medicine

基　　金：山东省医药卫生科技发展计划项目(202103011004)。

摘　　要：目的采用孟德尔随机化分析方法,探究参与心肌炎(MC)的相关免疫细胞。方法对全基因关联研究数据库(GWAS)进行数据挖掘,暴露因素为731种免疫细胞特征,结局因素为心肌炎。采用逆方差加权法(IVW)、MR-Egger法、Simple Mode法、加权中位数法和Weighted Mode法等回归模型进行孟德尔随机化分析。同时进行异质性检验、水平多效性分析、敏感性分析。通过逆方差加权法(IVW)对筛选出的相关免疫细胞特征进行多变量孟德尔随机化分析,以矫正7种阳性免疫细胞特征对结局的影响。结果(1)两样本孟德尔随机化IVW法结果显示:CD39+resting Treg%resting Treg(OR=1.237,95%CI:1.039~1.474)、CD4+CD8dim%leukocyte(OR=0.737,95%CI:0.543~0.100)、CD28-CD8dim AC(OR=0.868,95%CI:0.753~0.100)、CD28-CD8br AC(OR=1.398,95%CI:1.097~1.780)、CD20 on CD20-CD38-(OR=1.295,95%CI:1.012~1.659)、CCR2 on monocyte(OR=1.010,95%CI:1.000~1.208)、CD11b on basophil(OR=0.852,95%CI:0.727~0.998)7种免疫细胞特征与MC存在因果关系。(2)多变量孟德尔随机化结果显示,CD39+resting Treg%resting Treg(OR=1.228,95%CI:1.059~1.423)、CD28-CD8dim AC(OR=0.629,95%CI:0.428~0.924)、CCR2 on monocyte(OR=0.661,95%CI:0.488~0.895)与MC存在相关性。(3)反向孟德尔随机化结果未发现7种阳性免疫细胞特征与MC存在因果关系。结论本研究通过遗传学手段证实了免疫细胞与MC之间的密切联系,为今后的研究提供参考。Objective Using Mendelian randomization analysis to explore the immune cells involved in myocarditis(MC).Methods Genome-wide association study(GWAS)was used to mine the data,and the exposure factors were 731 immune cell traits,and the outcome factor was myocarditis.Regression models such as Inverse-Variance Weighted method(IVW),MR-Egger,Simple Mode,weighted median and Weighted Mode were used for Mendelian randomization analysis.At the same time,heterogeneity tests,horizontal multiple validity analyses,and sensitivity analyses were also conducted.Multivariate Mendelian randomization analysis of the relevant immune cell traits was performed by Inverse-Variance Weighted method(IVW)to correct the effect of seven positive immune cell traits on the outcome.Results(1)The results of Mendelian randomization showed that there was a causal relationship between 7 immune cell traits that include CD39+resting Treg%resting Treg(OR=1.237,95%CI:1.039-1.474),CD4+CD8dim%leukocyte(OR=0.737,95%CI:0.543-0.100),CD28-CD8dim AC(OR=0.868,95%CI:0.753-0.100),CD28-CD8br AC(OR=1.398,95%CI:1.097-1.780),CD20 on CD20-CD38-(OR=1.295,95%CI:1.012-1.659),CCR2 on monocyte(OR=1.010,95%CI:1.000-1.208),CD11b on basophil(OR=0.852,95%CI:0.727-0.998)and MC.(2)The results of multivariate Mendelian randomization showed that CD39+resting Treg%resting Treg(OR=1.228,95%CI:1.059-1.423),CD28-CD8dim AC(OR=0.629,95%CI:0.428-0.924),CCR2 on monocyte(OR=0.661,95%CI:0.488-0.895)were correlated with MC.(3)The results of reverse Mendelian randomization did not find a causal relationship between 7 positive immune signatures and MC.ConclusionThis study confirm the close relationship between immune cells and MC through genetics,which will provide a reference for future research.

关 键 词：孟德尔随机化 全基因组关联研究 心肌炎 免疫细胞 

分 类 号：R542.21[医药卫生—心血管疾病]