Analysis of the causal relationship between immune cells and rheumatoid arthritis from the perspective of genetic variation: a bidirectional two-sample Mendelian randomization study.
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引用次数: 0
Abstract
Background: Immune factors are crucial in the pathogenesis of rheumatoid arthritis (RA), and immune cells play a key role in the development of RA. However, there is still disagreement regarding the specific roles of each type of immune cell in the pathological process of RA.
Methods: This study used bidirectional two-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and RA. Utilizing publicly available genetic data, we initially treated immune cell characteristics as exposures to investigate their causal effects on the risk of RA. Subsequently, we performed reverse two-sample MR using the positively selected cells from the initial analysis as outcomes, aiming to identify the core immune cells involved. Finally, a comprehensive sensitivity analysis was conducted to validate the robustness, heterogeneity, and horizontal pleiotropy of the results.
Results: Using data from 731 immune cells as exposures and cell SNPs as instruments, we independently conducted two-sample MR analysis for each patient with RA. The main analytical method used was the IVW method, with a significance level set at P < 0.05 for inclusion. In total, we identified 42 immune cell phenotypes that were causally associated with the onset of RA. For the reverse MR analysis, we used RA as the exposure factor and focused on 42 immune cell phenotypes as outcomes. Our analysis revealed causal relationships between the onset of RA and 7 immune cell phenotypes. Among these, 6 showed positive causal relationships, while 1 exhibited a negative causal relationship.
Conclusions: Our study emphasized the causal relationship between immune cells and RA through bidirectional two-sample MR analysis, identifying the immune cells causally associated with RA.
背景:免疫因素在类风湿性关节炎(RA)的发病机制中起着关键作用,免疫细胞在RA的发病中起着关键作用。然而,关于各类免疫细胞在 RA 病理过程中的具体作用仍存在分歧:本研究采用双向双样本孟德尔随机分析法(MR)确定免疫细胞特征与 RA 之间的因果关系。利用可公开获得的遗传数据,我们首先将免疫细胞特征视为暴露,以研究其对 RA 风险的因果影响。随后,我们使用初始分析中正向选择的细胞作为结果,进行了反向双样本 MR 分析,旨在确定相关的核心免疫细胞。最后,我们进行了全面的敏感性分析,以验证结果的稳健性、异质性和水平多向性:以 731 个免疫细胞的数据为暴露,以细胞 SNPs 为工具,我们对每位 RA 患者独立进行了两组样本 MR 分析。采用的主要分析方法是 IVW 法,显著性水平设定为 P 结论:我们的研究强调了免疫细胞与 RA 患者之间的因果关系:我们的研究通过双向双样本磁共振分析强调了免疫细胞与 RA 之间的因果关系,确定了与 RA 有因果关系的免疫细胞。
期刊介绍:
Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication.
Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.