基于孟德尔随机化分析血清炎症因子与心房颤动的因果关系  

A Medelian Randomization Study of Causal Association between Serum Inflammatory Factors and Atrial Fibrillation

作　　者：何锦涛 罗立博 刘英健 薛玉梅[2] 饶芳 HE Jintao;LUO Libo;LIU Yingjian;XUE Yumei;RAO Fang(School of Medicine,South China University of Technology,Guangzhou 510080,China;Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China)

机构地区：[1]华南理工大学医学院,广州510080 [2]广东省心血管病研究所南方医科大学附属广东省人民医院(广东省医学科学院),广州510080

出　　处：《岭南心血管病杂志》2024年第2期191-196,共6页South China Journal of Cardiovascular Diseases

基　　金：国家自然科学基金(项目编号:82270321)。

摘　　要：目的采用两个样本的孟德尔随机化方法(Medelian randomization,MR)进行因果推断,探讨血清炎症因子与心房颤动(atrial fibrillation,AF)之间的潜在关联。方法本研究选择的91种血清炎症因子数据从一项对14824名欧洲血统健康受试者进行的全基因组关联研究(genome-wide association study,GWAS)中获得。有关AF的合并数据来自一项大型GWAS荟萃分析研究,纳入60620例欧洲祖先的患者和970216例对照。采用逆方差加权法(inverse variance weighting,IVW)、Egger回归法(MR-Egger regression,MR-Egger)、加权中位数法(weighted median estimate,WME)、简单中位数法(simple mode)和基于模式的估计法(weighted mode)等5种MR分析方法,另外采用MR-Egger、MR-PRESSO法、Cochran′s Q test检验和留一法(Leave-One-Out)作为敏感性分析方法。结果IVW方法发现,3个血清炎症因子与AF的发生、发展存在因果关系,分别是CD40L受体浓度(OR=0.947,95%CI:0.9160.978,P=0.001),成纤维细胞生长因子5(fibroblast growth factor 5,FGF5)浓度(OR=1.064,95%CI:1.0341.095,P<0.001),白血病抑制因子受体(leukemia inhibitory factor receptor,LIFR)浓度(OR=0.908,95%CI:0.866~0.951,P<0.001)。结论基于遗传数据的研究认为血清炎症因子CD40L受体、FGF5、LIFR与AF之间存在因果关联,有望为AF发生、发展提供敏感的生物标志物,并为干预炎症因子以治疗AF提供有价值的见解。Objectives To explore the potential association between serum inflammatory factors and atrial fibrillation(AF)by Medelian randomization(MR)using two-sample methods to perform causal inference.Methods Data on the 91 serum inflammatory factors selected for this study were obtained from a genome-wide association study(GWAS)of 14824 healthy subjects of European ancestry,and the combined data on AF were obtained from a large GWAS metaanalysis study including 60620 patients of European ancestry and 970216 controls.Five MR analysis methods,including inverse variance weighting(IVW),MR-Egger regression,weighted median estimate(WME),simple median estimate(simple mode),and weighted mode were applied.Additionally,sensitivity analyses included MR-Egger,MR-PRESSO,Cochran's Q test,and Leave-One-Out.Results The IVW method indicated causal relationships between 3 inflammatory factors,namely CD40L receptor concentrations(OR=0.947,95%CI:0.916-0.978,P=0.001),fibroblast growth factor 5(FGF5)concentrations(OR=1.064,95%CI:1.034-1.095,P<0.001),and leukemia inhibitory factor receptor(LIFR)concentrations(OR=0.908,95%CI:0.866-0.951,P<0.001),had causal association with the occurrence and development of AF.Conclusions Genetic data-based research suggests a causal association between serum inflammatory factors(CD40L receptor,FGF5 and LIFR)and AF.The study results provide sensitive biomarkers for the occurrence and development of AF,and valuable insights for the potential intervention of inflammatory factors in treating AF.

关 键 词：心房颤动 孟德尔随机化 炎症因子 因果关系 

分 类 号：R541.7[医药卫生—心血管疾病]