{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:37:20Z","timestamp":1780472240130,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Children with childhood\u2010onset rheumatoid arthritis (RA) include those with rheumatoid factor or anti\u2013citrullinated protein antibody\u2013positive juvenile idiopathic arthritis. To test the hypothesis that adult\u2010onset RA\u2013associated variants are also associated with childhood\u2010onset RA, we investigated RA\u2010associated variants at 5 loci in a cohort of patients with childhood\u2010onset RA. We also assessed the cumulative association of these variants in susceptibility to childhood\u2010onset RA using a weighted genetic risk score (wGRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 155 children with childhood\u2010onset RA and 684 healthy controls were genotyped for 5 variants in the <jats:italic>PTPN22<\/jats:italic>, <jats:italic>TRAF1\/C5<\/jats:italic>, <jats:italic>STAT4<\/jats:italic>, and <jats:italic>TNFAIP3<\/jats:italic> loci. High\u2010resolution HLA\u2013DRB1 genotypes were available for 149 cases and 373 controls. We tested each locus for association with childhood\u2010onset RA via logistic regression. We also computed a wGRS for each subject, with weights based on the natural log of the published odds ratios (ORs) for the alleles investigated, and used logistic regression to test the wGRS for association with childhood\u2010onset RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Childhood\u2010onset RA was associated with <jats:italic>TNFAIP3<\/jats:italic> rs10499194 (OR 0.60 [95% confidence interval 0.44\u20130.83]), <jats:italic>PTPN22<\/jats:italic> rs2476601 (OR 1.61 [95% confidence interval 1.11\u20132.31]), and <jats:italic>STAT4<\/jats:italic> rs7574865 (OR 1.41 [95% confidence interval 1.06\u20131.87]) variants. The wGRS was significantly different between cases and controls (<jats:italic>P<\/jats:italic> &lt; 2 \u00d7 10<jats:sup>\u221216<\/jats:sup>). Individuals in the third to fifth quintiles of wGRS had a significantly increased disease risk compared to baseline (individuals in the first quintile). Higher wGRS was associated with increased risk of childhood\u2010onset RA, especially among males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The magnitude and direction of the association between <jats:italic>TNFAIP3<\/jats:italic>, <jats:italic>STAT4<\/jats:italic>, and <jats:italic>PTPN22<\/jats:italic> variants and childhood\u2010onset RA are similar to those observed in RA, suggesting that adult\u2010onset RA and childhood\u2010onset RA share common genetic risk factors. Using a wGRS, we have demonstrated the cumulative association of RA\u2010associated variants with susceptibility to childhood\u2010onset RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37913","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T11:33:29Z","timestamp":1362137609000},"page":"1663-1667","source":"Crossref","is-referenced-by-count":27,"title":["Brief Report: Susceptibility to Childhood\u2010Onset Rheumatoid Arthritis: Investigation of a Weighted Genetic Risk Score That Integrates Cumulative Effects of Variants at Five Genetic Loci"],"prefix":"10.1002","volume":"65","author":[{"given":"Sampath","family":"Prahalad","sequence":"first","affiliation":[{"name":"Emory University and Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen N.","family":"Conneely","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"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":"Carol A.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital and Research Institute Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Ponder","sequence":"additional","affiliation":[{"name":"Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Rohani\u2010Pichavant","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Zwick","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila T.","family":"Angeles\u2010Han","sequence":"additional","affiliation":[{"name":"Emory University and Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry B.","family":"Vogler","sequence":"additional","affiliation":[{"name":"Emory University and Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Rouster\u2010Stevens","sequence":"additional","affiliation":[{"name":"Emory University and Children's Healthcare of Atlanta Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Wise","sequence":"additional","affiliation":[{"name":"Texas Scottish Rite Hospital for Children Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilynn","family":"Punaro","sequence":"additional","affiliation":[{"name":"Texas Scottish Rite Hospital for Children Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Reed","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D.","family":"Mellins","sequence":"additional","affiliation":[{"name":"Stanford University Medical Center Stanford California"}],"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":"David N.","family":"Glass","sequence":"additional","affiliation":[],"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"}]}],"member":"311","published-online":{"date-parts":[[2013,5,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.582"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33376"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000024"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.120170"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2462"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050853"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10370"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel170"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24618"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.27"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024380"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24328"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.37913","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.37913","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T11:44:49Z","timestamp":1696592689000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.37913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,30]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1002\/art.37913"],"URL":"https:\/\/doi.org\/10.1002\/art.37913","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,30]]}}}