炎症性关节病与心血管疾病因果关系的双向孟德尔随机化研究

Bidirectional Mendelian Randomization Study of the Causal Relationship between Inflammatory Joint Disease and Cardiovascular Disease

目的:探索炎症性关节病(IJD)与心血管疾病(CVD)的因果关系。方法:在全基因组关联研究(GWAS)中收集与IJD和CVD强相关的独立单核苷酸多态性(SNPs)作为工具变量(IVs)进行双向孟德尔随机化(MR)分析。MR分析采用逆方差加权法(IVW)作为主要方法,以加权中位数法(WME)、MR-Egger回归法(MER)、加权模型法(WM)和简单模型法(SM)进行辅助分析,评估IJD与CVD的因果关系,并进行敏感性分析以评估结果的稳健性。结果:本研究将IJD作为暴露因素共筛选到与CVD相关的10个SNP作为工具变量。IVW结果显示IJD和CVD之间存在正向因果关系(OR=2.14,95%CI:1.11~4.16,P=0.0230951,P<0.05)。Cochran’s Q检验显示不存在异质性(P>0.05),MR-Egger回归法未发现工具变量的水平多效性(P>0.05)。逐个剔除SNP后,MR分析结果稳健。MR分析显示IJD和CVD不支持反向因果关系(OR=0.99,95%CI:0.99~1.00,P=0.4686601,P>0.05)。结论:这项MR研究证明了IJD对CVD的存在因果关联,但反向因果关系是不成立的,旨在促进对IJD与CVD关系的认识,对于IJD患者可以考虑在疾病早期预防和临床干预CVD。

ObjectiveObjective:To explore the causal relationship between Inflammatory joint disease(IJD)and cardiovascular disease(CVD).MethodsMethods:Single nucleotide polymorphisms(SNPs)strongly associated with IJD and CVD were collected as instrumental variables(IVs)in a genome-wide as‐sociation study(GWAS).Inverse variance weighted(IVW)was employed as the primary approach for conducting MR analysis,while auxiliary analy‐ses were performed using weighted median(WME),MR-Egger regression(MER),weighted mode(WM),and simple mode(SM)to assess the causal relationship between IJD and CVD.Sensitivity analyses were performed to assess the robustness of the result.ResultsResults:The present study considered IJD as an exposure variable,utilizing a set of 10 SNPs associated with CVD as instrumental variables.IVW results showed a positive causal relation‐shipn between IJD and CVD(OR=2.14,95%CI:1.11~4.16,P=0.0230951,P<0.05).Cochran's Q test showed no heterogeneity(P>0.05),and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables(P>0.05).The MR analysis results were robust after removing SNP one by one.MR analysis shows that IJD and CVD do not support a reverse causal relationship(OR=0.99,95%CI:0.99~1.00,P=0.4686601,P>0.05).ConclusionConclusion:This MR study demonstrates the causal relationship between IJD and CVD,but the reverse causal relationship is not established.The aim is to promote understanding of the relationship between IJD and CVD,aand early prevention and clinical intervention for CVD should be consid‐ered in IJD patients.