{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:50:10Z","timestamp":1781020210143,"version":"3.54.1"},"reference-count":34,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_rir-2025-0005_s_101\">\n                  <jats:title>Background and Objective<\/jats:title>\n                  <jats:p>Multiple studies have shown a substantial association between obstructive sleep apnea (OSA) and rheumatic disease. However, traditional studies are susceptible to confounding factors or reverse causal relationships, and the exact causal relationship still needs to be clearly defined. This study aims to use a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between OSA and rheumatoid immune diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0005_s_102\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a two-sample bidirectional MR analysis by using large-scale genome-wide association studies (GWAS) summary statistics to investigate whether there is a causal relationship between OSA and rheumatic disease. Inverse variance weighted (IVW) was used as the primary analysis approach, supplemented by MR-Egger and Weighted median methods. Sensitivity analyses were conducted to ensure the robustness of the results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0005_s_103\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The MR predicted ankylosing spondylitis (AS) was associated with risk of OSA (IVW: OR = 1.0239, 95% CI = 1.0086 to 1.0394, <jats:italic>P<\/jats:italic> = 0.0021; MR-Egger: OR = 1.0374, 95% CI = 1.0089 to 1.0668, <jats:italic>P<\/jats:italic> = 0.0326; weighted median: OR = 1.0287, 95% CI = 1.0109 to 1.0467, <jats:italic>P<\/jats:italic> = 0.0014). However, no bidirectional causal association was found between other rheumatic disease and OSA. The sensitivity analysis confirmed the robustness of the results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0005_s_104\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our analysis suggests a potential causal relationship between AS and OSA. There was no direct causal relationship between OSA and other rheumatic disease. We need more experimental research on specific pathological and physiological mechanisms in the future.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/rir-2025-0005","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T07:52:04Z","timestamp":1743666724000},"page":"42-51","source":"Crossref","is-referenced-by-count":2,"title":["The causal relationship between obstructive sleep apnea and rheumatic disease: A bidirectional Mendelian randomization study"],"prefix":"10.1515","volume":"6","author":[{"given":"Ming","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Rheumatology & Immunology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , Zhejiang Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , Zhejiang Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"2025040307331989098_j_rir-2025-0005_ref_001","doi-asserted-by":"crossref","unstructured":"Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70\u201381.","DOI":"10.1016\/j.smrv.2016.07.002"},{"key":"2025040307331989098_j_rir-2025-0005_ref_002","doi-asserted-by":"crossref","unstructured":"Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323:1389\u20131400.","DOI":"10.1001\/jama.2020.3514"},{"key":"2025040307331989098_j_rir-2025-0005_ref_003","doi-asserted-by":"crossref","unstructured":"de Lima FF, Mazzotti DR, Tufik S, et al. The role inflammatory response genes in obstructive sleep apnea syndrome: a review. Sleep Breath. 2016;20:331\u2013338.","DOI":"10.1007\/s11325-015-1226-7"},{"key":"2025040307331989098_j_rir-2025-0005_ref_004","doi-asserted-by":"crossref","unstructured":"Kang JH, Lin HC. Obstructive sleep apnea and the risk of autoimmune diseases: a longitudinal population-based study. Sleep Med. 2012;13:583\u2013588.","DOI":"10.1016\/j.sleep.2012.03.002"},{"key":"2025040307331989098_j_rir-2025-0005_ref_005","doi-asserted-by":"crossref","unstructured":"Chung WS, Lin CL. Sleep disorders associated with risk of rheumatoid arthritis. Sleep Breath. 2018;22:1083\u20131091.","DOI":"10.1007\/s11325-018-1639-1"},{"key":"2025040307331989098_j_rir-2025-0005_ref_006","doi-asserted-by":"crossref","unstructured":"Chen WS, Chang YS, Chang CC, et al. Management and Risk Reduction of Rheumatoid Arthritis in Individuals with Obstructive Sleep Apnea: A Nationwide Population-Based Study in Taiwan. Sleep. 2016;39:1883\u20131890.","DOI":"10.5665\/sleep.6174"},{"key":"2025040307331989098_j_rir-2025-0005_ref_007","doi-asserted-by":"crossref","unstructured":"Zeng Z, Jin T, Ni J, et al. Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study. Semin Arthritis Rheum. 2022;57:152095.","DOI":"10.1016\/j.semarthrit.2022.152095"},{"key":"2025040307331989098_j_rir-2025-0005_ref_008","doi-asserted-by":"crossref","unstructured":"Yang YW, Kang JH, Lin HC. Increased risk of psoriasis following obstructive sleep apnea: a longitudinal population-based study. Sleep Med. 2012;13:285\u2013289.","DOI":"10.1016\/j.sleep.2011.07.018"},{"key":"2025040307331989098_j_rir-2025-0005_ref_009","doi-asserted-by":"crossref","unstructured":"Shen TC, Hang LW, Liang SJ, et al. Risk of obstructive sleep apnoea in patients with rheumatoid arthritis: a nationwide population-based retrospective cohort study. BMJ Open. 2016;6:e013151.","DOI":"10.1136\/bmjopen-2016-013151"},{"key":"2025040307331989098_j_rir-2025-0005_ref_010","doi-asserted-by":"crossref","unstructured":"Wali S, Mustafa M, Manzar D, et al. Prevalence of obstructive sleep apnea in patients with rheumatoid arthritis. J Clin Sleep Med. 2020;16:259\u2013265.","DOI":"10.5664\/jcsm.8178"},{"key":"2025040307331989098_j_rir-2025-0005_ref_011","doi-asserted-by":"crossref","unstructured":"Yeh TC, Chen WS, Chang YS, et al. Risk of obstructive sleep apnea in patients with Sj\u00f6gren syndrome and Beh\u00e7et\u2019s disease: a nationwide, population-based cohort study. Sleep Breath. 2020;24:1199\u20131205.","DOI":"10.1007\/s11325-019-01953-w"},{"key":"2025040307331989098_j_rir-2025-0005_ref_012","doi-asserted-by":"crossref","unstructured":"Meidan R, Elalouf O, Tauman R, et al. Systemic Lupus Erythem-50 atous and Obstructive Sleep Apnea: A Possible Association. Life (Basel). 2023;13:697.","DOI":"10.3390\/life13030697"},{"key":"2025040307331989098_j_rir-2025-0005_ref_013","doi-asserted-by":"crossref","unstructured":"Singh JA, Cleveland JD. Gout and the Risk of Incident Obstructive Sleep Apnea in Adults 65 Years or Older: An Observational Study. J Clin Sleep Med. 2018;14:1521\u20131527.","DOI":"10.5664\/jcsm.7328"},{"key":"2025040307331989098_j_rir-2025-0005_ref_014","doi-asserted-by":"crossref","unstructured":"Egeberg A, Khalid U, Gislason GH, et al. Psoriasis and Sleep Apnea: A Danish Nationwide Cohort Study. J Clin Sleep Med. 2016;12:663\u2013671.","DOI":"10.5664\/jcsm.5790"},{"key":"2025040307331989098_j_rir-2025-0005_ref_015","doi-asserted-by":"crossref","unstructured":"Gundogdu S, Borekci S, Atahan E, et al. Increased frequency of obstructive sleep apnea in the patients with systemic sclerosis. Sleep Breath. 2021;25:237\u2013242","DOI":"10.1007\/s11325-020-02080-7"},{"key":"2025040307331989098_j_rir-2025-0005_ref_016","doi-asserted-by":"crossref","unstructured":"Solak O, Fidan F, D\u00fcndar U, et al. The prevalence of obstructive sleep apnoea syndrome in ankylosing spondylitis patients. Rheumatology (Oxford). 2009;48:433\u2013435.","DOI":"10.1093\/rheumatology\/kep021"},{"key":"2025040307331989098_j_rir-2025-0005_ref_017","doi-asserted-by":"crossref","unstructured":"Tsao CH, Huang JY, Huang HH, et al. Ankylosing Spondylitis Is Associated With Risk of New-Onset Obstructive Sleep Apnea: A Nationwide Population-Based Cohort Study. Front Med (Lausanne). 2019;6:285.","DOI":"10.3389\/fmed.2019.00285"},{"key":"2025040307331989098_j_rir-2025-0005_ref_018","doi-asserted-by":"crossref","unstructured":"Mirrakhimov AE. Obstructive sleep apnea and autoimmune rheumatic disease: is there any link? Inflamm Allergy Drug Targets. 2013;12:362\u2013367.","DOI":"10.2174\/18715281113129990051"},{"key":"2025040307331989098_j_rir-2025-0005_ref_019","doi-asserted-by":"crossref","unstructured":"Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133\u20131163.","DOI":"10.1002\/sim.3034"},{"key":"2025040307331989098_j_rir-2025-0005_ref_020","doi-asserted-by":"crossref","unstructured":"Smith GD, Ebrahim S. \u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1\u201322.","DOI":"10.1093\/ije\/dyg070"},{"key":"2025040307331989098_j_rir-2025-0005_ref_021","doi-asserted-by":"crossref","unstructured":"Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res. 2017;26:2333\u20132355.","DOI":"10.1177\/0962280215597579"},{"key":"2025040307331989098_j_rir-2025-0005_ref_022","doi-asserted-by":"crossref","unstructured":"Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40:740\u2013752.","DOI":"10.1093\/ije\/dyq151"},{"key":"2025040307331989098_j_rir-2025-0005_ref_023","doi-asserted-by":"crossref","unstructured":"Bowden J, Davey Smith G, Haycock PC, et al. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40:304\u2013314.","DOI":"10.1002\/gepi.21965"},{"key":"2025040307331989098_j_rir-2025-0005_ref_024","doi-asserted-by":"crossref","unstructured":"Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44:512\u2013525.","DOI":"10.1093\/ije\/dyv080"},{"key":"2025040307331989098_j_rir-2025-0005_ref_025","doi-asserted-by":"crossref","unstructured":"Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.","DOI":"10.7554\/eLife.34408"},{"key":"2025040307331989098_j_rir-2025-0005_ref_026","doi-asserted-by":"crossref","unstructured":"Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693\u2013698.","DOI":"10.1038\/s41588-018-0099-7"},{"key":"2025040307331989098_j_rir-2025-0005_ref_027","doi-asserted-by":"crossref","unstructured":"Nolte IM. Metasubtract: an R-package to analytically produce leave-one-out meta-analysis GWAS summary statistics. Bioinformatics. 2020;36:4521\u20134522.","DOI":"10.1093\/bioinformatics\/btaa570"},{"key":"2025040307331989098_j_rir-2025-0005_ref_028","doi-asserted-by":"crossref","unstructured":"Shi T, Min M, Sun C, et al. A meta-analysis of the association between gout, serum uric acid level, and obstructive sleep apnea. Sleep Breath. 2019;23:1047\u20131057.","DOI":"10.1007\/s11325-019-01827-1"},{"key":"2025040307331989098_j_rir-2025-0005_ref_029","doi-asserted-by":"crossref","unstructured":"Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369: 1379\u20131390.","DOI":"10.1016\/S0140-6736(07)60635-7"},{"key":"2025040307331989098_j_rir-2025-0005_ref_030","doi-asserted-by":"crossref","unstructured":"Zhang X, Sun Z, Zhou A, et al. Association Between Infections and Risk of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis. Front Immunol. 2021;12:768741.","DOI":"10.3389\/fimmu.2021.768741"},{"key":"2025040307331989098_j_rir-2025-0005_ref_031","doi-asserted-by":"crossref","unstructured":"Yang TH, Xirasagar S, Cheng YF, et al. Association of cervical spondylosis with obstructive sleep apnea. Sleep Med. 2020;71:54\u201358.","DOI":"10.1016\/j.sleep.2020.03.025"},{"key":"2025040307331989098_j_rir-2025-0005_ref_032","doi-asserted-by":"crossref","unstructured":"Neelapu BC, Kharbanda OP, Sardana HK, et al. Craniofacial and upper airway morphology in adult obstructive sleep apnea patients: A systematic review and meta-analysis of cephalometric studies. Sleep Med Rev. 2017;31:79\u201390.","DOI":"10.1016\/j.smrv.2016.01.007"},{"key":"2025040307331989098_j_rir-2025-0005_ref_033","doi-asserted-by":"crossref","unstructured":"Hoffman K, Mansoor E, Panhwar MS, et al. Prevalence of Obstructive Sleep Apnea Is Increased in Patients With Inflammatory Bowel Disease: A Large, Multi-Network Study. Crohns Colitis 360. 2022;4:otac026.","DOI":"10.1093\/crocol\/otac026"},{"key":"2025040307331989098_j_rir-2025-0005_ref_034","doi-asserted-by":"crossref","unstructured":"Walsh JA, Song X, Kim G, et al. Evaluation of the comorbidity burden in patients with ankylosing spondylitis using a large US administrative claims data set. Clin Rheumatol. 2018;37:1869\u20131878.","DOI":"10.1007\/s10067-018-4086-2"}],"container-title":["Rheumatology and Immunology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/rir-2025-0005\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/rir-2025-0005\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T07:53:19Z","timestamp":1743666799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/rir-2025-0005\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,4,2]]},"published-print":{"date-parts":[[2025,4,2]]}},"alternative-id":["10.1515\/rir-2025-0005"],"URL":"https:\/\/doi.org\/10.1515\/rir-2025-0005","relation":{},"ISSN":["2719-4523"],"issn-type":[{"value":"2719-4523","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,1]]}}}