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
陈思 1曾小莉 1聂睿 1廖华 2潘丽丽 2袁慧1
作者信息
- 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
- 折叠
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.
Abstract
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Key words
Rheumatoid arthritis/Giant cell arteritis/Mendelian randomization/Causal relationship引用本文复制引用
基金项目
国家重点研发计划(2022YFC2009600)
国家重点研发计划(2022YFC2009602)
北京市重大疫情防治重点专科建设项目(2022)()
STI2030重大项目(2021ZD0200600201ZD020063)
出版年
2024
NETL
NSTL
万方数据