PDF(Pubmed)
Abstract：
UNASSIGNED: Several observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa.
UNASSIGNED: We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings.
UNASSIGNED: In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations.
UNASSIGNED: This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.
UNASSIGNED: We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings.
UNASSIGNED: In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations.
UNASSIGNED: This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.
摘要：
■一些观察性研究表明类风湿性关节炎（RA）与支气管扩张之间存在关联。然而，这些条件之间是否存在因果关系尚待确定。这项研究旨在调查遗传预测的RA是否与支气管扩张的风险相关，反之亦然。
■我们从FinnGen联盟获得了RA全基因组关联研究（GWAS）数据，以及来自IEUOpenGWAS项目的支气管扩张GWAS数据。单变量孟德尔随机化(MR)分析采用逆方差加权(IVW)估计作为主要方法。此外，双向和复制MR分析，多变量MR(MVMR)，中介分析,并进行了敏感性分析以验证研究结果.
■在UVMR分析中，IVW结果显示RA的支气管扩张风险增加(OR=1.18,95%CI=1.10-1.27;p=2.34×10-6).在反向MR分析中，未发现支气管扩张对RA风险有因果影响的证据.相反，在复制MR分析中，RA仍然与支气管扩张的风险增加相关。在调整非甾体抗炎药（NSAIDs）和糖皮质激素的处方后，MVMR分析中的估计值保持一致。发现免疫抑制剂可介导RA对支气管扩张的58％的作用。敏感性分析证实了这些关联的稳定性。
■这项研究表明RA与支气管扩张风险增加之间存在正的因果关系，为早期预防RA患者支气管扩张提供见解，并为免疫抑制剂作为介质在促进RA对支气管扩张的作用中的潜在作用提供新的思路。
■我们从FinnGen联盟获得了RA全基因组关联研究（GWAS）数据，以及来自IEUOpenGWAS项目的支气管扩张GWAS数据。单变量孟德尔随机化(MR)分析采用逆方差加权(IVW)估计作为主要方法。此外，双向和复制MR分析，多变量MR(MVMR)，中介分析,并进行了敏感性分析以验证研究结果.
■在UVMR分析中，IVW结果显示RA的支气管扩张风险增加(OR=1.18,95%CI=1.10-1.27;p=2.34×10-6).在反向MR分析中，未发现支气管扩张对RA风险有因果影响的证据.相反，在复制MR分析中，RA仍然与支气管扩张的风险增加相关。在调整非甾体抗炎药（NSAIDs）和糖皮质激素的处方后，MVMR分析中的估计值保持一致。发现免疫抑制剂可介导RA对支气管扩张的58％的作用。敏感性分析证实了这些关联的稳定性。
■这项研究表明RA与支气管扩张风险增加之间存在正的因果关系，为早期预防RA患者支气管扩张提供见解，并为免疫抑制剂作为介质在促进RA对支气管扩张的作用中的潜在作用提供新的思路。
