Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study
Background: Pulmonary arterial hypertension (PAH) is a severe vascular disorder with a multifactorial etiology, including potential genetic predispositions. Understanding the causal relationship between autoimmune diseases and the risk of developing PAH can inform clinical strategies for prevention...
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| Language: | English |
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Ubiquity Press
2025-07-01
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| Series: | Global Heart |
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| Online Access: | https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1445 |
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| author | Chao Ma Cheng Gong Bin Wang Yangmeina Li Yongxiang Qian Xiaoying Zhang Dongmei Di Min Wang |
| author_facet | Chao Ma Cheng Gong Bin Wang Yangmeina Li Yongxiang Qian Xiaoying Zhang Dongmei Di Min Wang |
| author_sort | Chao Ma |
| collection | DOAJ |
| description | Background: Pulmonary arterial hypertension (PAH) is a severe vascular disorder with a multifactorial etiology, including potential genetic predispositions. Understanding the causal relationship between autoimmune diseases and the risk of developing PAH can inform clinical strategies for prevention and treatment. Methods: We conducted a two-sample Mendelian Randomization (MR) analysis to evaluate the causal effect of genetic predisposition to five autoimmune diseases (systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], inflammatory bowel disease [IBD], multiple sclerosis [MS], and type 1 diabetes [T1D]) on the risk of PAH. This involved employing various MR methods (IVW, MR-Egger, Weighted median, Simple mode, and Weighted mode), as well as conducting tests for heterogeneity and horizontal pleiotropy. Results: The analysis revealed a significant association between genetic predisposition to RA and IBD with an increased risk of PAH (RA: OR = 1.28, 95% CI [1.01–1.61], p = 0.042; IBD: OR = 1.29, 95% CI [1.01–1.64], p = 0.043). However, no association was observed between genetically determined MS, SLE, and T1D with the risk of PAH (MS: p = 0.876; SLE: p = 0.564; T1D: p = 0.061). Additionally, tests for heterogeneity and pleiotropy provided no evidence of their influence, suggesting the robustness of these associations. Reverse MR analysis also indicated no significant effect of PAH on the genetic susceptibility to these autoimmune diseases. Conclusion: The findings suggest a possible genetic causative link between RA and IBD and the risk of developing PAH. Conversely, genetic predisposition to MS, SLE, and T1D does not appear to influence PAH risk. Understanding these relationships may offer insights into the pathophysiology of PAH and inform screening strategies within at-risk populations. |
| format | Article |
| id | doaj-art-6238b888548c44fdb02d42fbaf08456b |
| institution | Kabale University |
| issn | 2211-8179 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Ubiquity Press |
| record_format | Article |
| series | Global Heart |
| spelling | doaj-art-6238b888548c44fdb02d42fbaf08456b2025-08-21T12:35:35ZengUbiquity PressGlobal Heart2211-81792025-07-01201585810.5334/gh.14451426Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization StudyChao Ma0https://orcid.org/0009-0001-3668-7161Cheng Gong1https://orcid.org/0009-0004-3641-9484Bin Wang2Yangmeina Li3https://orcid.org/0009-0002-3546-5708Yongxiang Qian4Xiaoying Zhang5Dongmei Di6Min Wang7https://orcid.org/0000-0002-5624-6363Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Otolaryngology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province 213003Background: Pulmonary arterial hypertension (PAH) is a severe vascular disorder with a multifactorial etiology, including potential genetic predispositions. Understanding the causal relationship between autoimmune diseases and the risk of developing PAH can inform clinical strategies for prevention and treatment. Methods: We conducted a two-sample Mendelian Randomization (MR) analysis to evaluate the causal effect of genetic predisposition to five autoimmune diseases (systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], inflammatory bowel disease [IBD], multiple sclerosis [MS], and type 1 diabetes [T1D]) on the risk of PAH. This involved employing various MR methods (IVW, MR-Egger, Weighted median, Simple mode, and Weighted mode), as well as conducting tests for heterogeneity and horizontal pleiotropy. Results: The analysis revealed a significant association between genetic predisposition to RA and IBD with an increased risk of PAH (RA: OR = 1.28, 95% CI [1.01–1.61], p = 0.042; IBD: OR = 1.29, 95% CI [1.01–1.64], p = 0.043). However, no association was observed between genetically determined MS, SLE, and T1D with the risk of PAH (MS: p = 0.876; SLE: p = 0.564; T1D: p = 0.061). Additionally, tests for heterogeneity and pleiotropy provided no evidence of their influence, suggesting the robustness of these associations. Reverse MR analysis also indicated no significant effect of PAH on the genetic susceptibility to these autoimmune diseases. Conclusion: The findings suggest a possible genetic causative link between RA and IBD and the risk of developing PAH. Conversely, genetic predisposition to MS, SLE, and T1D does not appear to influence PAH risk. Understanding these relationships may offer insights into the pathophysiology of PAH and inform screening strategies within at-risk populations.https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1445pulmonary arterial hypertensionautoimmune diseasesrheumatoid arthritisinflammatory bowel diseasemendelian randomization |
| spellingShingle | Chao Ma Cheng Gong Bin Wang Yangmeina Li Yongxiang Qian Xiaoying Zhang Dongmei Di Min Wang Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study Global Heart pulmonary arterial hypertension autoimmune diseases rheumatoid arthritis inflammatory bowel disease mendelian randomization |
| title | Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study |
| title_full | Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study |
| title_fullStr | Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study |
| title_full_unstemmed | Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study |
| title_short | Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study |
| title_sort | exploring the causal link between autoimmune diseases and pulmonary arterial hypertension a bidirectional mendelian randomization study |
| topic | pulmonary arterial hypertension autoimmune diseases rheumatoid arthritis inflammatory bowel disease mendelian randomization |
| url | https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1445 |
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