巨细胞动脉炎与类风湿关节炎的因果关系:一项孟德尔随机化研究  

The Causal Relationship Between Giant Cell Arteritis and Rheumatoid Arthritis:a Mendelian Randomization Study

作　　者：陈思 曾小莉[1] 聂睿 廖华[2] 潘丽丽[2] 袁慧[1] CHEN Si;ZENG Xiaoli;NIE Rui;LIAO Hua;PAN Lili;YUAN Hui(Department of Clinical Laboratory,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Department of Rheumatology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院检验科,北京100029 [2]首都医科大学附属北京安贞医院风湿免疫科,北京100029

出　　处：《标记免疫分析与临床》2024年第7期1177-1182,1188,共7页Labeled Immunoassays and Clinical Medicine

基　　金：国家重点研发计划(编号:2022YFC2009600,2022YFC2009602);“北京市重大疫情防治重点专科项目”(2022);STI2030重大项目(编号:2021ZD0200600201ZD020063)。

摘　　要：目的探索巨细胞动脉炎(GCA)与类风湿关节炎(RA)之间的双向因果关系。方法GCA和RA的全基因组关联研究(GWAS)数据集来自FinnGen数据库,采用双向孟德尔随机化(MR)分析来探讨GCA与RA之间的因果关系,研究结果通过验证数据集和荟萃分析进行进一步验证。采用随机效应逆方差加权法(IVW)、加权中位数法、MR Egger回归、简单和加权模型进行双向MR分析,并进行敏感性检验。结果训练阶段结果表明RA会增加GCA的患病风险(IVW:OR=1.44;95%CI 1.25~1.65,P=2.20×10^(-7)),且这种因果关系在4个验证集(所有IVW:P<0.001)及荟萃分析(IVW:OR=1.37,95%CI 1.29~1.45,P<0.0001)中得到了验证。此外,反向MR分析3个验证集(所有IVW:P<0.001)及荟萃分析(IVW:OR=1.05,95%CI 1.03~1.08,P<0.0001)的结果表明GCA会增加RA的患病风险。结论GCA与RA之间存在双向的因果关联,这对疾病的临床管理具有重要意义。Objective To explore the bidirectional causal relationship between Giant Cell Arteritis(GCA)and Rheumatoid Arthritis(RA).Methods The genome-wide association study(GWAS)datasets for GCA and RA were obtained from FinnGen database.A bidirectional Mendelian Randomization(MR)analysis was conducted to investigate the causal relationship between GCA and RA.The study results were further validated using independent datasets and meta-analysis.The bidirectional MR analysis was performed using inverse variance weighted(IVW)random effects model,weighted median,MR Egger,and simple and weighted mode models,with sensitivity tests conducted to ensure robustness.Results In the discovery phase,RA was found to increase the risk of GCA(IVW:OR=1.44;95%CI 1.25-1.65,P=2.20×10^(-7)),and this causal relationship was validated by using four independent datasets(all IVW P<0.001),as well as confirmed by meta-analysis(IVW:OR=1.37,95%CI 1.29-1.45,P<0.0001).Furthermore,the reverse MR analysis indicated that GCA could increase the risk of RA in three validation datasets(all IVW P<0.001)and meta-analysis(IVW:OR=1.05,95%CI 1.03-1.08,P<0.0001).Conclusion There is a bidirectional causal relationship between GCA and RA,which could have significant implications for the clinical management of these diseases.

关 键 词：类风湿关节炎 巨细胞动脉炎 孟德尔随机化 因果关系 

分 类 号：R593.22[医药卫生—内科学]