{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:15:15Z","timestamp":1789881315739,"version":"4.0.1"},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,30]],"date-time":"2008-12-30T00:00:00Z","timestamp":1230595200000},"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":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well\u2010established genetic factors known to contribute to JIA susceptibility, <jats:italic>HLA<\/jats:italic> and <jats:italic>PTPN22<\/jats:italic>, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A genome\u2010wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single\u2010nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort (n = 2,024). In one region in which association was confirmed, fine\u2010mapping was performed (654 cases and 1,847 controls).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the <jats:italic>HLA<\/jats:italic> region, while the second strongest association was with a SNP within the <jats:italic>VTCN1<\/jats:italic> gene. Fine\u2010mapping of that gene was performed, and 10 SNPs were found to be associated with JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to successfully apply a SNP\u2010based genome\u2010wide association approach to the investigation of JIA. The replicated association with markers in the <jats:italic>VTCN1<\/jats:italic> gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24179","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T21:41:14Z","timestamp":1230759674000},"page":"258-263","source":"Crossref","is-referenced-by-count":70,"title":["Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome\u2010wide association analysis"],"prefix":"10.1002","volume":"60","author":[{"given":"Anne","family":"Hinks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Shephard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Eyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bowes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cargill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayi","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"British Society of Paediatric and Adolescent Rheumatology Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia C.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Worthington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,30]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1991","article-title":"Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997","volume":"25","author":"Petty RE","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar591"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05911"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2088"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109557"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.32"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.27"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00152-3"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.24179","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.24179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:25:10Z","timestamp":1696983910000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.24179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,30]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1002\/art.24179"],"URL":"https:\/\/doi.org\/10.1002\/art.24179","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,30]]}}}