Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-08-29 DOI:10.1186/s12876-024-03319-3

Hai-Ping Zhang, Zhe Zhou, Ke Chen, Li-Fen Xiong, Jun Wu, Lei Jin

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引用次数: 0

Abstract

Background: An association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis.

Methods: The genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran's Q value, respectively.

Results: PBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method.

Conclusions: Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.

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原发性胆汁性胆管炎对全身性风湿病有因果关系：孟德尔随机研究。

背景：观察性研究发现，原发性胆汁性胆管炎（PBC）与系统性风湿性疾病（SRDs）之间存在关联，但确切的因果关系仍不清楚。我们的目的是通过孟德尔随机化（MR）分析评估原发性胆汁性胆管炎对 SRDs 的因果影响：全基因组关联研究（GWAS）摘要数据来自 MRC IEU OpenGWAS 和 FinnGen 数据库。选择 PBC 的独立遗传变异作为工具变量。主要采用反方差加权法评估 PBC 对锡琼综合征（SS）、类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、系统性硬化症（SSc）、混合结缔组织病（MCTD）和多发性肌炎（PM）的因果效应。水平多向性和异质性分别通过 MR-Egger 截距检验和 Cochran's Q 值进行测量：结果：PBC对SS（OR=1.177，P=8.02e-09）、RA（OR=1.071，P=9.80e-04）、SLE（OR=1.447，P=1.04e-09）、SSc（OR=1.399，P=2.52e-04）、MCTD（OR=1.306，P=4.92e-14）和PM（OR=1.416，P=1.16e-04）具有因果效应。根据 MR-Egger 截距检验，横向多效性不存在（所有 P 值均大于 0.05）。我们的研究结果的稳健性通过 "留一剔除 "法得到了进一步提高：我们的研究为 PBC 和 SRD 提供了新的见解，表明了对各种 SRD 的偶然影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464