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Rheumatology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Juvenile idiopathic arthritis (<jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content>) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> have rheumatoid factor (<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>)\u2013positive arthritis, which phenotypically resembles adult rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). Our objective was to compare and contrast the genetics of <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> with those of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> and selected other <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> (n = 340) and controls (n = 14,412) were genotyped using the Immunochip array. Single\u2010nucleotide polymorphisms were tested for association using a logistic regression model adjusting for admixture proportions. We calculated weighted genetic risk scores (<jats:styled-content style=\"fixed-case\">wGRS<\/jats:styled-content>) of reported <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> risk loci, and we compared the ability of these <jats:styled-content style=\"fixed-case\">wGRS<\/jats:styled-content> to predict <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As expected, the <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> region was strongly associated with <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> (<jats:italic>P<\/jats:italic> = 5.51 \u00d7 10<jats:sup>\u221231<\/jats:sup>). Nineteen of 44 <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> risk loci and 6 of 27 oligoarticular\/<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010negative polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> risk loci were associated with <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> (<jats:italic>P<\/jats:italic> &lt; 0.05). The <jats:styled-content style=\"fixed-case\">RA wGRS<\/jats:styled-content> predicted <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> (area under the curve [<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>] 0.71) better than did the oligoarticular\/<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010negative polyarticular <jats:styled-content style=\"fixed-case\">JIA wGRS<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> 0.59). The genetic profile of patients with <jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> was more similar to that of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients with age at onset 16\u201329 years than to that of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> patients with age at onset \u226570 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010positive polyarticular <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> is genetically more similar to adult <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> than to the most common <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> categories and thus appears to be a childhood\u2010onset presentation of autoantibody\u2010positive <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40443","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T18:46:39Z","timestamp":1518201999000},"page":"957-962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Brief Report: The Genetic Profile of Rheumatoid Factor\u2013Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-3967","authenticated-orcid":false,"given":"Anne","family":"Hinks","sequence":"first","affiliation":[{"name":"University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda C.","family":"Marion","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Cobb","sequence":"additional","affiliation":[{"name":"University of Manchester and Central Manchester University Hospitals NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Comeau","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Sudman","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Ainsworth","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bowes","sequence":"additional","affiliation":[{"name":"University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Juvenile Idiopathic Arthritis Consortium for Immunochip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara L.","family":"Becker","sequence":"additional","affiliation":[{"name":"Children's Mercy Kansas City Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Bohnsack","sequence":"additional","affiliation":[{"name":"University of Utah Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes\u2010Peter","family":"Haas","sequence":"additional","affiliation":[{"name":"German Centre for Pediatric and Adolescent Rheumatology Garmisch\u2010Partenkirchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D.","family":"Mellins","sequence":"additional","affiliation":[{"name":"Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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M.","family":"Yeung","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children and University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl D.","family":"Langefeld","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Thomson","sequence":"additional","affiliation":[{"name":"University of Manchester and Central Manchester University Hospitals NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampath","family":"Prahalad","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,21]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27516"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3204"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2614"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37913"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33376"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-10-29"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210025"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2462"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.094052.109"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000529"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq419"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1076"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1885"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12873"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210324"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40443","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40443","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:11:35Z","timestamp":1759925495000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,21]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/art.40443"],"URL":"https:\/\/doi.org\/10.1002\/art.40443","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,21]]},"assertion":[{"value":"2017-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}