Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China.
Department of Radiology, The Affiliated Hospital of Wuhan Sports University, Wuhan, 430079, China.
BMC Gastroenterol. 2024 Aug 29;24(1):294. doi: 10.1186/s12876-024-03319-3.
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.
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.
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.
Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.
在观察性研究中，原发性胆汁性胆管炎（PBC）与系统性风湿病（SRD）之间存在关联，但确切的因果关系尚不清楚。我们旨在通过孟德尔随机化（MR）分析评估 PBC 对 SRD 的因果影响。
从 MRC IEU OpenGWAS 和 FinnGen 数据库中获得了全基因组关联研究（GWAS）汇总数据。选择独立的 PBC 遗传变异作为工具变量。逆方差加权法被用作评估 PBC 对干燥综合征（SS）、类风湿关节炎（RA）、系统性红斑狼疮（SLE）、系统性硬皮病（SSc）、混合性结缔组织病（MCTD）和多发性肌炎（PM）的因果影响的主要方法。MR-Egger 截距检验和 Cochran's Q 值分别用于衡量水平多效性和异质性。
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）有因果影响。基于 MR-Egger 截距检验，不存在水平多效性（所有 P 值均>0.05）。通过单倍体缺失方法进一步增强了我们结果的稳健性。
我们的研究为 PBC 和 SRD 提供了新的见解，表明其对各种 SRD 具有因果影响。
