摘要
目的探讨循环免疫细胞表型和冠心病是否存在因果关系。方法以循环免疫细胞表型作为暴露因素,冠心病作为结局事件,将与循环免疫细胞表型和冠心病密切相关的单核苷酸多态性(SNPs)作为遗传工具变量,采用两样本孟德尔随机化分析方法对全基因关联研究(GWAS)数据进行分析。循环免疫细胞表型和冠心病的GWAS数据均来源于在线GWAS数据库。分析方法主要为逆方差加权法(IVW),此外还包括简单模式法(simple mode)、加权中位数法(weighted median)、加权模式法(weighted mode)和MR Egger。以比值比(odds ratio,OR)和95%置信区间(95%CI)评估循环免疫细胞与冠心病的因果关系。为避免反向因果关系,将冠心病作为暴露因素,上述循环免疫细胞表型作为结局事件,进行反向孟德尔随机化分析。结果本研究筛选出731种循环免疫细胞表型进行孟德尔随机化分析,IVW方法显示,18种循环免疫细胞表型与冠心病存在因果关系,并且其余MR Egger等方法结果与IVW方向一致。其中12种循环免疫细胞表型与冠心病风险增加有显著因果关系,6种循环免疫细胞表型显著降低冠心病风险。MR-Egger回归结果表明,不存在遗传多效性影响(P>0.05)。反向分析发现,冠心病对CD45标记的自然杀伤T水平升高存在显著因果关系,而对IgD^(-)CD24^(-)标记B淋巴细胞水平降低存在显著因果关系。结论多种T、B细胞亚群对冠心病发病风险具有显著影响。此外,冠心病对CD45标记的自然杀伤T以及IgD^(-)CD24^(-)标记B淋巴细胞水平变化均存在显著影响。本研究关注特定的免疫细胞的不同效应功能及其引发的细胞反应,并强调针对B细胞功能进行治疗的潜在策略。
Objective To explore whether there is a causal relationship between circulating immune cell phenotype and coronary heart disease.Methods The circulating immune cell phenotype was used as the exposure factor and coronary heart disease as the outcome event,single nucleotide polymorphisms(SNPs)closely related to the circulating immune cell phenotype and coronary heart disease were used as genetic instrumental variables.Two sample Mendelian randomization analysis was used to analyze the genome-wide association study(GWAS)data.GWAS data for the circulating immune cell phenotype and coronary heart disease were both sourced from the online GWAS database.The main analysis methods included inverse variance weighted(IVW),as well as simple mode,weighted median,weighted mode,and MR-Egger.The causal relationship between circulating immune cells and coronary heart disease was evaluated by odds ratio(OR)and 95% confidence interval(95%CI).Coronary heart disease was used as an exposure factor,and the above circulating immune cell phenotypes were used as the outcome event for reverse Mendelian randomization analysis in order to avoid reverse causality.Results This study screened 731 circulating immune cell phenotypes for Mendelian randomization analysis.The IVW method showed a causal relationship between 18 circulating immune cell phenotypes and coronary heart disease,and the results of other MR Egger methods were consistent with the direction of IVW.Among them,12 circulating immune cell phenotypes had a significant causal relationship with an increased risk of coronary heart disease,while 6 circulating immune cell phenotypes significantly reduced the risk of coronary heart disease.The MR-Egger regression results indicated that there was no genetic pleiotropy effect(P>0.05).Reverse analysis revealed a significant causal relationship of coronary heart disease with an increase in CD45 labeled natural killer T levels and a decrease in IgD^(-)CD24^(-)labeled B lymphocyte levels.Conclusions Multiple subsets of T and B cells have a sign
作者
袁航
王大英
Yuan Hang;Wang Daying(Cardiovascular Medicine Department,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China)
出处
《中国急救医学》
CAS
CSCD
2024年第5期436-442,共7页
Chinese Journal of Critical Care Medicine
关键词
循环免疫表型
冠心病
孟德尔随机化
基因证据
因果关系
Circulating immune cell phenotype
Coronary heart disease
Mendelian randomization
Genetic evidence
Causal relationship
