Deng Zongqi, Lei Wanyang, Kuang Xiao, Liu Xiaoxiao, Tai Wenlin
Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People's Republic of China.
Department of Clinical Laboratory, the Northeast Yunnan Central Hospital of Kunming Medical University, Northeast Yunnan Central Hospital, Kunming, Yunnan, People's Republic of China.
Clin Exp Gastroenterol. 2025 Jun 17;18:139-148. doi: 10.2147/CEG.S500542. eCollection 2025.
Observational studies indicated potential associations between primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the causal relationship between RA and PBC remains unclear and controversial. The aim of this study was to evaluate the causal relationships among seropositive RA (SPRA), seronegative RA (SNRA) and PBC.
This study employed a Mendelian randomization (MR) framework to analyze genome-wide association study (GWAS) data from a European population. The dataset included 802 cases and 16,489 controls for PBC, 18,019 cases and 991,604 controls for SPRA, and 8,515 cases and 1,015,471 controls for SNRA, retrieved on June 11, 2024. Instrumental variables (IVs) were selected based on genome-wide significance (P < 5.0E-08) and independence (R < 0.001). Palindromic and incompatible SNPs were excluded, and weak instruments (F < 10) were removed. Inverse variance weighting (IVW) was the primary analysis method, complemented by Bayesian weighted MR (BWMR), robustly adjusted profile scores (MR-RAPS), MR-Egger, and weighted median approaches. Sensitivity analyses included Cochran's Q test, MR-Egger regression, MR-PRESSO global test, and leave-one-out analysis to assess the robustness of the results.
SPRA increased the risk of genetic susceptibility to PBC (OR=1.28, 95% CI 1.10-1.4, =0.001). No causal effect of the SNRA on PBC risk was observed.
Our findings show that SPRA increases the risk of developing with PBC. This will help inform future screening guidelines for associated PBC in patients with RA.
观察性研究表明原发性胆汁性胆管炎（PBC）与类风湿关节炎（RA）之间存在潜在关联。然而，RA与PBC之间的因果关系仍不明确且存在争议。本研究的目的是评估血清阳性RA（SPRA）、血清阴性RA（SNRA）和PBC之间的因果关系。
本研究采用孟德尔随机化（MR）框架分析来自欧洲人群的全基因组关联研究（GWAS）数据。数据集包括2024年6月11日检索到的802例PBC病例和16489例对照、18019例SPRA病例和991604例对照，以及8515例SNRA病例和1015471例对照。基于全基因组显著性（P < 5.0E - 08）和独立性（R < 0.001）选择工具变量（IVs）。排除回文和不相容的单核苷酸多态性（SNPs），并去除弱工具变量（F < 10）。逆方差加权（IVW）是主要分析方法，辅以贝叶斯加权MR（BWMR）、稳健调整轮廓评分（MR - RAPS）、MR - Egger和加权中位数方法。敏感性分析包括Cochran's Q检验、MR - Egger回归、MR - PRESSO全局检验和留一法分析，以评估结果的稳健性。
SPRA增加了PBC遗传易感性风险（OR = 1.28，95%CI 1.10 - 1.4，P = 0.001）。未观察到SNRA对PBC风险有因果效应。
我们的研究结果表明，SPRA增加了发生PBC的风险。这将有助于为未来RA患者相关PBC的筛查指南提供信息。
