Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study
Zongqi Deng,1,* Wanyang Lei,2,* Xiao Kuang,1 Xiaoxiao Liu,1 Wenlin Tai1 1Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical L...
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Dove Medical Press
2025-06-01
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| author | Deng Z Lei W Kuang X Liu X Tai W |
| author_facet | Deng Z Lei W Kuang X Liu X Tai W |
| author_sort | Deng Z |
| collection | DOAJ |
| description | Zongqi Deng,1,&ast; Wanyang Lei,2,&ast; Xiao Kuang,1 Xiaoxiao Liu,1 Wenlin Tai1 1Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, the Northeast Yunnan Central Hospital of Kunming Medical University, Northeast Yunnan Central Hospital, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlin Tai, Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email taiwenlin@kmmu.edu.cnBackground: 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.Keywords: primary biliary cholangitis, rheumatoid arthritis, causal effect, Mendelian randomization |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-8c8b8795d309481aae8028e60b93a66b2025-08-20T03:29:49ZengDove Medical PressClinical and Experimental Gastroenterology1178-70232025-06-01Volume 18Issue 1139148103951Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization StudyDeng Z0Lei W1Kuang X2Liu X3Tai W4Department of Clinical Laboratory, Yunnan Molecular Diagnostic CenterDepartment of Clinical Laboratory, Yunnan Molecular Diagnostic CenterDepartment of Clinical Laboratory, Yunnan Molecular Diagnostic CenterDepartment of Clinical Laboratory, Yunnan Molecular Diagnostic CenterDepartment of Clinical Laboratory, Yunnan Molecular Diagnostic CenterZongqi Deng,1,&ast; Wanyang Lei,2,&ast; Xiao Kuang,1 Xiaoxiao Liu,1 Wenlin Tai1 1Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, the Northeast Yunnan Central Hospital of Kunming Medical University, Northeast Yunnan Central Hospital, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlin Tai, Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email taiwenlin@kmmu.edu.cnBackground: 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.Keywords: primary biliary cholangitis, rheumatoid arthritis, causal effect, Mendelian randomizationhttps://www.dovepress.com/primary-biliary-cholangitis-and-seropositive-rheumatoid-arthritis-a-tw-peer-reviewed-fulltext-article-CEGPrimary biliary cholangitisRheumatoid arthritisCausal effectMendelian randomization |
| spellingShingle | Deng Z Lei W Kuang X Liu X Tai W Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study Clinical and Experimental Gastroenterology Primary biliary cholangitis Rheumatoid arthritis Causal effect Mendelian randomization |
| title | Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study |
| title_full | Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study |
| title_fullStr | Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed | Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study |
| title_short | Primary Biliary Cholangitis and Seropositive Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study |
| title_sort | primary biliary cholangitis and seropositive rheumatoid arthritis a two sample mendelian randomization study |
| topic | Primary biliary cholangitis Rheumatoid arthritis Causal effect Mendelian randomization |
| url | https://www.dovepress.com/primary-biliary-cholangitis-and-seropositive-rheumatoid-arthritis-a-tw-peer-reviewed-fulltext-article-CEG |
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