Zongqi Deng, Wanyang Lei, Xiao Kuang, Xiaoxiao Liu, Wenlin Tai
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Instrumental variables (IVs) were selected based on genome-wide significance (P < 5.0E-08) and independence (R<sup>2</sup> < 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.</p><p><strong>Results: </strong>SPRA increased the risk of genetic susceptibility to PBC (OR=1.28, 95% CI 1.10-1.4, <i>P</i> =0.001). No causal effect of the SNRA on PBC risk was observed.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"18 ","pages":"139-148"},"PeriodicalIF":2.5000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183510/pdf/","citationCount":"0","resultStr":"{\"title\":\"Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study.\",\"authors\":\"Zongqi Deng, Wanyang Lei, Xiao Kuang, Xiaoxiao Liu, Wenlin Tai\",\"doi\":\"10.2147/CEG.S500542\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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. 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引用次数: 0
摘要
背景:观察性研究表明原发性胆道胆管炎(PBC)和类风湿关节炎(RA)之间存在潜在关联。然而,RA和PBC之间的因果关系尚不清楚,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)与PBC之间的因果关系。方法: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。该数据集包括802例PBC和16489例对照,18019例SPRA和8515例SNRA和1015471例对照,检索时间为2024年6月11日。工具变量的选择基于全基因组显著性(P < 0.05 -08)和独立性(R2 < 0.001)。排除回文和不相容的snp,去除弱仪器(F < 10)。反方差加权(IVW)是主要的分析方法,辅以贝叶斯加权MR (BWMR)、稳健调整剖面评分(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全局检验和留一分析,以评估结果的稳健性。结果:SPRA增加了PBC遗传易感性的风险(OR=1.28, 95% CI 1.10-1.4, P =0.001)。没有观察到SNRA对PBC风险的因果影响。结论:我们的研究结果表明,SPRA增加了合并PBC的风险。这将有助于为RA患者相关PBC的未来筛查指南提供信息。
Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study.
Background: 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.
Methods: 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 (R2 < 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.
Results: SPRA increased the risk of genetic susceptibility to PBC (OR=1.28, 95% CI 1.10-1.4, P =0.001). No causal effect of the SNRA on PBC risk was observed.
Conclusion: 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.