Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study
Fei Wang,1 Dengxu Jiang,2 Zhong Zhang,2 Zhengjun Hu,2 Yijian Liang1 1Department of Spinal Surgery, Chengdu BOE Hospital, Chengdu, People’s Republic of China; 2Department of Orthopaedics, The Third People’s Hospital of Chengdu/The Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’...
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Dove Medical Press
2025-07-01
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| Series: | Journal of Pain Research |
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| Online Access: | https://www.dovepress.com/causal-effects-of-inflammatory-arthritis-subtypes-on-fibromyalgia-a-co-peer-reviewed-fulltext-article-JPR |
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| author | Wang F Jiang D Zhang Z Hu Z Liang Y |
| author_facet | Wang F Jiang D Zhang Z Hu Z Liang Y |
| author_sort | Wang F |
| collection | DOAJ |
| description | Fei Wang,1 Dengxu Jiang,2 Zhong Zhang,2 Zhengjun Hu,2 Yijian Liang1 1Department of Spinal Surgery, Chengdu BOE Hospital, Chengdu, People’s Republic of China; 2Department of Orthopaedics, The Third People’s Hospital of Chengdu/The Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of ChinaCorrespondence: Yijian Liang, Department of Spinal Surgery, Chengdu BOE Hospital, Chengdu, 610200, People’s Republic of China, Email yijiancq@163.comPurpose: Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain and central sensitization, often co-occurring with inflammatory arthritis (IA) in clinical presentation. While observational studies suggest a higher prevalence of FM among IA patients, the causal relationship between IA and FM remains uncertain due to potential confounding factors and the possibility of reverse causation.Patients and Methods: We employed a two-sample Mendelian randomization (TSMR) approach to evaluate the causal effect of nine IA subtypes on FM, utilizing genetic summary data from large-scale genome-wide association studies (GWAS) encompassing up to 201,581 participants (exposure: IA phenotypes) and 168,378 participants (outcome: FM). The primary analysis was conducted using the Inverse-Variance Weighted (IVW) method, with sensitivity analyses assessing robustness and pleiotropy.Results: MR analysis revealed significant causal links between several IA subtypes and FM. Rheumatoid arthritis (OR 1.105, 95% CI 1.020– 1.198), enteropathic arthritis (OR 1.207, 95% CI 1.123– 1.299), Juvenile Idiopathic Arthritis (OR 1.307, 95% CI 1.183– 1.445), and other IA subtypes showed an increased risk of FM (all p< 0.0001). Psoriatic arthritis demonstrated no significant association with FM (OR 1.006, 95% CI 0.909– 1.112, p=0.911). Sensitivity analyses confirmed no significant heterogeneity and consistent results, despite minor horizontal pleiotropy observed in MR-Egger regression.Conclusion: This study provides genetic evidence supporting a causal relationship between IA subtypes and an increased risk of FM. However, no significant causal link was found between psoriatic arthritis and FM. These findings emphasize the role of immune-mediated inflammation in FM pathogenesis and highlight the differential impact of various IA subtypes on FM risk.Keywords: fibromyalgia, inflammatory arthritis, Mendelian randomization, genetic association, rheumatoid arthritis, psoriatic arthritis |
| format | Article |
| id | doaj-art-6f4c3ca2f0f344cebe800c361bdebc76 |
| institution | Kabale University |
| issn | 1178-7090 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Dove Medical Press |
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| series | Journal of Pain Research |
| spelling | doaj-art-6f4c3ca2f0f344cebe800c361bdebc762025-08-20T03:58:36ZengDove Medical PressJournal of Pain Research1178-70902025-07-01Volume 18Issue 138053817105334Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization StudyWang F0Jiang D1Zhang Z2Hu Z3Liang Y4Department of Spinal SurgeryDepartment of OrthopaedicsDepartment of OrthopaedicsDepartment of OrthopaedicsDepartment of Spinal SurgeryFei Wang,1 Dengxu Jiang,2 Zhong Zhang,2 Zhengjun Hu,2 Yijian Liang1 1Department of Spinal Surgery, Chengdu BOE Hospital, Chengdu, People’s Republic of China; 2Department of Orthopaedics, The Third People’s Hospital of Chengdu/The Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of ChinaCorrespondence: Yijian Liang, Department of Spinal Surgery, Chengdu BOE Hospital, Chengdu, 610200, People’s Republic of China, Email yijiancq@163.comPurpose: Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain and central sensitization, often co-occurring with inflammatory arthritis (IA) in clinical presentation. While observational studies suggest a higher prevalence of FM among IA patients, the causal relationship between IA and FM remains uncertain due to potential confounding factors and the possibility of reverse causation.Patients and Methods: We employed a two-sample Mendelian randomization (TSMR) approach to evaluate the causal effect of nine IA subtypes on FM, utilizing genetic summary data from large-scale genome-wide association studies (GWAS) encompassing up to 201,581 participants (exposure: IA phenotypes) and 168,378 participants (outcome: FM). The primary analysis was conducted using the Inverse-Variance Weighted (IVW) method, with sensitivity analyses assessing robustness and pleiotropy.Results: MR analysis revealed significant causal links between several IA subtypes and FM. Rheumatoid arthritis (OR 1.105, 95% CI 1.020– 1.198), enteropathic arthritis (OR 1.207, 95% CI 1.123– 1.299), Juvenile Idiopathic Arthritis (OR 1.307, 95% CI 1.183– 1.445), and other IA subtypes showed an increased risk of FM (all p< 0.0001). Psoriatic arthritis demonstrated no significant association with FM (OR 1.006, 95% CI 0.909– 1.112, p=0.911). Sensitivity analyses confirmed no significant heterogeneity and consistent results, despite minor horizontal pleiotropy observed in MR-Egger regression.Conclusion: This study provides genetic evidence supporting a causal relationship between IA subtypes and an increased risk of FM. However, no significant causal link was found between psoriatic arthritis and FM. These findings emphasize the role of immune-mediated inflammation in FM pathogenesis and highlight the differential impact of various IA subtypes on FM risk.Keywords: fibromyalgia, inflammatory arthritis, Mendelian randomization, genetic association, rheumatoid arthritis, psoriatic arthritishttps://www.dovepress.com/causal-effects-of-inflammatory-arthritis-subtypes-on-fibromyalgia-a-co-peer-reviewed-fulltext-article-JPRFibromyalgiaInflammatory ArthritisMendelian RandomizationGenetic AssociationRheumatoid ArthritisPsoriatic Arthritis |
| spellingShingle | Wang F Jiang D Zhang Z Hu Z Liang Y Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study Journal of Pain Research Fibromyalgia Inflammatory Arthritis Mendelian Randomization Genetic Association Rheumatoid Arthritis Psoriatic Arthritis |
| title | Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study |
| title_full | Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study |
| title_fullStr | Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study |
| title_full_unstemmed | Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study |
| title_short | Causal Effects of Inflammatory Arthritis Subtypes on Fibromyalgia: A Comprehensive Mendelian Randomization Study |
| title_sort | causal effects of inflammatory arthritis subtypes on fibromyalgia a comprehensive mendelian randomization study |
| topic | Fibromyalgia Inflammatory Arthritis Mendelian Randomization Genetic Association Rheumatoid Arthritis Psoriatic Arthritis |
| url | https://www.dovepress.com/causal-effects-of-inflammatory-arthritis-subtypes-on-fibromyalgia-a-co-peer-reviewed-fulltext-article-JPR |
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