{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:19:22Z","timestamp":1780316362852,"version":"3.54.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although numerous observational studies have indicated a potential association between autoimmune diseases, such as rheumatoid arthritis (RA) and alopecia areata (AA), the research reports lack a clear causal relationship. In this study, our objective is to utilize the Mendelian randomization (MR) design to examine the potential causal association between RA and AA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the causal relationship between RA and AA, we utilized large-scale gene aggregation data from genome-wide association studies (GWAS), including RA (n=58,284) and AA (n=361,822) based on previous observational studies. In our analysis, we mainly employed the inverse variance-weighted (IVW) method of the random effects model, supplemented by the weighted median (WM) method and the MR Egger method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The findings from the IVW methods revealed a significant association between genetically predicted RA and an increased likelihood of AA, as evidenced by an odds ratio of 1.21 (95%CI = 1.11-1.32; <jats:italic>P<\/jats:italic> &amp;lt; 0.001. Both the WM method and MR-Egger regression consistently showed significant directional outcomes (Both <jats:italic>P<\/jats:italic> &amp;lt; 0.05), indicating a robust association between RA and AA. Additionally, both the funnel plot and the MR-Egger intercepts provided evidence of the absence of directional pleiotropy, suggesting that the observed association is not influenced by other common genetic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of the study suggest a possible link between genetically predicted RA and AA. This finding highlights the importance for individuals diagnosed with RA to remain vigilant and aware of the potential development of AA. Regular monitoring and early detection can be crucial in managing and addressing this potential complication.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1269640","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:10:34Z","timestamp":1698750634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Association between genetically predicted rheumatoid arthritis and alopecia areata: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Shengdong","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"New Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2013.3049","article-title":"Autoimmune, atopic, and mental health comorbid conditions associated with alopecia areata in the United States","volume":"149","author":"Huang","year":"2013","journal-title":"JAMA Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070","article-title":"'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease","volume":"32","author":"Smith","year":"2003","journal-title":"Int J Epidemiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"Haycock PC. The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219065","article-title":"Large-scale meta-analysis across East Asian and European populations updated genetic architecture and variant-driven biology of rheumatoid arthritis, identifying 11 novel susceptibility loci","volume":"80","author":"Ha","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2018","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int J Epidemiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7221","article-title":"A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating statistical power in Mendelian randomization studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int J Epidemiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579","article-title":"A review of instrumental variable estimators for Mendelian randomization","volume":"26","author":"Burgess","year":"2017","journal-title":"Stat Methods Med Res"},{"key":"B18","article-title":"Alopecia areata and autoimmunity","volume":"143","author":"Grandolfo","year":"2008","journal-title":"Giornale Italiano Di Dermatologia E Venereologia Organo Ufficiale Societa Italiana Di Dermatologia E Sifilografia."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3985","article-title":"Organ specificity in autoimmune diseases: thyroid and islet autoimmunity in alopecia areata","volume":"100","author":"Noso","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00150","article-title":"Impact of rheumatoid arthritis on alopecia: a nationwide population-based cohort study in Taiwan","volume":"7","author":"Chang","year":"2020","journal-title":"Front Med (Lausanne)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.109447","article-title":"Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis","volume":"69","author":"Patsopoulos","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e278","DOI":"10.1371\/journal.pmed.0040278","article-title":"A candidate gene approach identifies the TRAF1\/C5 region as a risk factor for rheumatoid arthritis","volume":"4","author":"Kurreeman","year":"2007","journal-title":"PloS Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09598.x","article-title":"The TRAF1\/C5 locus confers risk for familial and severe alopecia areata","volume":"162","author":"Redler","year":"2010","journal-title":"Br J Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.11.2421","article-title":"Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers","volume":"127","author":"Lin","year":"2000","journal-title":"Dev (Cambridge England)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0898-9","article-title":"Notch4, a non-HLA gene in the MHC is strongly associated with the most severe form of alopecia areata","volume":"112","author":"Tazi-Ahnini","year":"2003","journal-title":"Hum Genet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2013.01.002","article-title":"Genetic evidence for the involvement of NOTCH4 in rheumatoid arthritis and alopecia areata","volume":"150","author":"AlFadhli","year":"2013","journal-title":"Immunol Lett"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5966","DOI":"10.1038\/ncomms6966","article-title":"Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci","volume":"6","author":"Betz","year":"2015","journal-title":"Nat Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus placebo or adalimumab in rheumatoid arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"New Engl J Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00726-8","article-title":"Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach","volume":"18","author":"Tanaka","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3685","article-title":"Inhibiting Janus kinases to treat alopecia areata","volume":"20","author":"Divito","year":"2014","journal-title":"Nat Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3645","article-title":"Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition","volume":"20","author":"Xing","year":"2014","journal-title":"Nat Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41467-022-35264-8","article-title":"Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis","volume":"14","author":"Moon","year":"2023","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050177","article-title":"Mendelian randomisation and causal inference in observational epidemiology","volume":"5","author":"Sheehan","year":"2008","journal-title":"PloS Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ (Clinical Res ed.)."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1269640\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:10:37Z","timestamp":1698750637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1269640\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2023.1269640"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1269640","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"article-number":"1269640"}}