类风湿关节炎与中风风险的因果关系：一项孟德尔随机化研究。

Causal association between rheumatoid arthritis and risk of stroke: A Mendelian randomization study.

机构信息

Department of Rheumatism and Immunology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Jinghu District, Wuhu, Anhui 241001, China.

出版信息

Clin Neurol Neurosurg. 2024 Sep;244:108465. doi: 10.1016/j.clineuro.2024.108465. Epub 2024 Jul 21.

DOI:10.1016/j.clineuro.2024.108465

PMID:39059285

Abstract

BACKGROUND

Active rheumatoid arthritis (RA) may damage vascular endothelial cells, thereby increasing the likelihood of adverse cardiovascular events. However, it is not yet clearly established whether RA also increases the risk of adverse cerebrovascular events, particularly stroke.

OBJECTIVE

This study was designed to evaluate the likelihood of a causal association between RA and stroke.

METHOD

A two-sample Mendelian randomization (MR) analysis was performed using the inverse variance-weighted (IVW) average, weighted median, and MR-Egger regression methods. The analysis utilized publicly available summary statistics datasets from Genome-wide association studies (GWAS) meta-analyses for RA in individuals of European descent (total n = 484,598; case = 5427, control = 479,171) as the exposure cohort, and from GWAS meta-analyses for "vascular/heart problems diagnosed by doctor: stroke" in individuals included in the UK Biobank (total n = 461,880; case = 7055, control = 454,825, MRC-IEU consortium) as the outcome cohort.

RESULTS

Eight single-nucleotide polymorphisms with genome-wide significance were selected from the GWASs on RA as the instrumental variables. The results of the MR-Egger and weighted median analyses showed no causal association between RA and stroke (OR = 1.081, 95 % CI [0.943-1.240], P = 0.304) vs. OR = 1.079, 95 % CI [0.988-1.179], P = 0.091), respectively. However, the inverse variance-weighted (IVW) analysis results revealed a causal association between RA and stroke (OR = 1.115, 95 % CI [1.040-1.194], P = 0.002). Cochran's Q test and MR-Egger regression revealed no evidence of heterogeneity and horizontal pleiotropy.

CONCLUSION

The MR analysis results indicated that rheumatoid arthritis (RA) may be causally associated with an increased risk of stroke.

摘要

背景

活动性类风湿关节炎（RA）可能会损伤血管内皮细胞，从而增加不良心血管事件的发生风险。然而，RA 是否也会增加不良脑血管事件（尤其是中风）的发生风险，目前尚不清楚。

目的

本研究旨在评估 RA 与中风之间是否存在因果关联。

方法

采用两样本孟德尔随机化（MR）分析，使用逆方差加权（IVW）平均、加权中位数和 MR-Egger 回归方法。分析使用了来自欧洲血统个体的 RA 全基因组关联研究（GWAS）荟萃分析的公开可用汇总统计数据集（总 n = 484598；病例=5427，对照=479171）作为暴露队列，以及来自 UK Biobank 中包含的个体的“由医生诊断的血管/心脏问题：中风”的 GWAS 荟萃分析（总 n = 461880；病例=7055，对照=454825，MRC-IEU 联盟）作为结局队列。

结果

从 RA 的 GWAS 中选择了 8 个具有全基因组意义的单核苷酸多态性作为工具变量。MR-Egger 和加权中位数分析的结果均显示，RA 与中风之间没有因果关系（OR=1.081，95%CI[0.943-1.240]，P=0.304）与 OR=1.079，95%CI[0.988-1.179]，P=0.091）。然而，逆方差加权（IVW）分析结果显示 RA 与中风之间存在因果关系（OR=1.115，95%CI[1.040-1.194]，P=0.002）。Cochran's Q 检验和 MR-Egger 回归均未发现异质性和水平多效性的证据。