Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Rheumatology and Immunology, Center for General Practice Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Int J Rheum Dis. 2024 May;27(5):e15151. doi: 10.1111/1756-185X.15151.
Observational studies have found an association between autoimmune liver disease (AILD) and Sjögren's syndrome (SS). However, the causal relationship between the two remains unknown. Clinical guidelines indicate that the coexistence of AILD with other autoimmune diseases may impact prognosis and quality of life; hence, early recognition and management of extrahepatic autoimmune diseases is particularly crucial. Against this backdrop, this study aimed to utilize Mendelian randomization (MR) methods to investigate the potential causal relationship between AILD and SS.
We extracted summary statistics on AILD and SS from publicly available genome-wide association studies (GWAS) databases to identify appropriate instrumental variables (IVs). The inverse-variance weighted (IVW) method was utilized as the primary approach, with the weighted median (WM) method and MR-Egger method employed as supplementary methods to evaluate the potential causal relationship between the two conditions. Sensitivity analyses, including Cochran's Q test, MR-polynomial residuals and outliers (MR-PRESSO), MR-Egger intercept test, and the leave-one-out test, were performed to assess the stability of the results.
The MR study results indicate a significant causal relationship between PBC and PSC with the risk of SS in the European population (IVW: odds ratio [OR] = 1.155, 95% confidence interval [CI]: 1.092-1.222, p < .001; IVW: OR = 1.162, 95% CI: 1.051-1.284, p = .003). A series of sensitivity analyses have confirmed the reliability of the results.
Our study indicates that the presence of both PBC and PSC increases the susceptibility to SS. However, no reliable causal relationship was found between SS and the risk of PBC or PSC. These findings contribute to elucidating the potential pathogenic mechanisms of the disease and are of significant importance for the management of patients with PBC and PSC.
观察性研究发现自身免疫性肝病（AILD）与干燥综合征（SS）之间存在关联。然而，两者之间的因果关系尚不清楚。临床指南表明，AILD 与其他自身免疫性疾病同时存在可能会影响预后和生活质量；因此，早期识别和管理肝外自身免疫性疾病尤为重要。在此背景下，本研究旨在利用孟德尔随机化（MR）方法探讨 AILD 与 SS 之间潜在的因果关系。
我们从公开的全基因组关联研究（GWAS）数据库中提取了 AILD 和 SS 的汇总统计数据，以确定合适的工具变量（IVs）。采用逆方差加权（IVW）法作为主要方法，同时采用加权中位数（WM）法和 MR-Egger 法作为补充方法，以评估两种情况下的潜在因果关系。采用 Cochran's Q 检验、MR-多项式残差和异常值（MR-PRESSO）、MR-Egger 截距检验和逐一剔除检验等敏感性分析来评估结果的稳定性。
MR 研究结果表明，在欧洲人群中，PBC 和 PSC 与 SS 风险之间存在显著的因果关系（IVW：比值比[OR] = 1.155，95%置信区间[CI]：1.092-1.222，p < .001；IVW：OR = 1.162，95% CI：1.051-1.284，p = .003）。一系列敏感性分析证实了结果的可靠性。
本研究表明，同时存在 PBC 和 PSC 会增加患 SS 的易感性。然而，SS 与 PBC 或 PSC 风险之间没有可靠的因果关系。这些发现有助于阐明疾病的潜在发病机制，对 PBC 和 PSC 患者的管理具有重要意义。
