类风湿关节炎与支气管扩张症之间的因果关系:一项双向孟德尔随机化研究。

Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study.

机构信息

Department of Respiratory and Critical Care Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Department of Rheumatology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

出版信息

Arthritis Res Ther. 2024 May 23;26(1):104. doi: 10.1186/s13075-024-03336-3.

Abstract

BACKGROUND

Epidemiological observational studies have elucidated a correlation between rheumatoid arthritis (RA) and bronchiectasis. However, the causal nature of this association remains ambiguous. To clarify this potential causal linkage, we conducted a two-sample Mendelian randomization (MR) analysis to explore the bidirectional causality between RA and bronchiectasis.

METHODS

Summary statistics for RA and bronchiectasis were obtained from the IEU OpenGWAS database We employed various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode, to explore potential causal links between RA and bronchiectasis. Additionally, a series of sensitivity studies, such as Cochran's Q test, MR Egger intercept test, and leave-one-out analysis, were conducted to assess the MR analysis's accuracy further.

RESULTS

In the forward MR analysis, the primary analysis indicated that a genetic predisposition to RA correlated with an increased risk of bronchiectasis in European populations (IVW odds ratio (OR): 1.28, 95% confidence interval (CI): 1.20-1.37, p = 1.18E-13). Comparable results were noted in the East Asian subjects (IVW OR: 1.55, 95% CI: 1.30-1.34, p = 8.33E-07). The OR estimates from the other four methods were consistent with those obtained from the IVW method. Sensitivity analysis detected no evidence of horizontal pleiotropy or heterogeneity. Conversely, in the reverse MR analysis, we found no evidence to support a genetic causality between bronchiectasis and RA in either European or East Asian populations.

CONCLUSION

This study indicates that genetic predisposition to RA correlates with a heightened risk of bronchiectasis in both European and East Asian populations. These results imply that routine screening for bronchiectasis in RA patients could be beneficial, and effective management of RA may contribute to a reduced risk of bronchiectasis. Future research should aim to clarify the underlying mechanisms linking these two conditions.

摘要

背景

流行病学观察性研究已经阐明了类风湿关节炎(RA)和支气管扩张之间存在相关性。然而,这种关联的因果性质尚不清楚。为了阐明这种潜在的因果联系,我们进行了两样本孟德尔随机化(MR)分析,以探讨 RA 和支气管扩张之间的双向因果关系。

方法

从 IEU OpenGWAS 数据库中获取 RA 和支气管扩张的汇总统计数据。我们采用了多种方法,包括逆方差加权(IVW)、MR-Egger、加权中位数、加权众数和简单众数,来探索 RA 和支气管扩张之间潜在的因果关系。此外,还进行了一系列敏感性研究,如 Cochran's Q 检验、MR Egger 截距检验和逐一剔除分析,以进一步评估 MR 分析的准确性。

结果

在正向 MR 分析中,主要分析表明,RA 的遗传易感性与欧洲人群中支气管扩张的风险增加相关(IVW 比值比(OR):1.28,95%置信区间(CI):1.20-1.37,p=1.18E-13)。在东亚人群中也观察到了类似的结果(IVW OR:1.55,95% CI:1.30-1.34,p=8.33E-07)。其他四种方法的 OR 估计值与 IVW 方法一致。敏感性分析未发现水平多效性或异质性的证据。相反,在反向 MR 分析中,我们在欧洲和东亚人群中均未发现支气管扩张和 RA 之间存在遗传因果关系的证据。

结论

本研究表明,RA 的遗传易感性与欧洲和东亚人群中支气管扩张的风险增加相关。这些结果表明,在 RA 患者中常规筛查支气管扩张可能有益,而有效管理 RA 可能有助于降低支气管扩张的风险。未来的研究应旨在阐明这两种疾病之间的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a2/11112812/a2383449b8f6/13075_2024_3336_Fig1_HTML.jpg

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