{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:00:46Z","timestamp":1787504446899,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","award":["VS0518"],"award-info":[{"award-number":["VS0518"]}],"id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023396","name":"Centre for Epidemiology Versus Arthritis, University of Manchester","doi-asserted-by":"publisher","award":["21755"],"award-info":[{"award-number":["21755"]}],"id":[{"id":"10.13039\/501100023396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M004600\/1"],"award-info":[{"award-number":["MR\/M004600\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R013926\/1"],"award-info":[{"award-number":["MR\/R013926\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["19612"],"award-info":[{"award-number":["19612"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20659"],"award-info":[{"award-number":["20659"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20747"],"award-info":[{"award-number":["20747"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["20542"],"award-info":[{"award-number":["20542"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["20621"],"award-info":[{"award-number":["20621"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21593"],"award-info":[{"award-number":["21593"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["22084"],"award-info":[{"award-number":["22084"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Juvenile idiopathic arthritis (JIA)\u2013associated uveitis (JIAU) is a serious JIA comorbidity that can result in vision impairment. This study aimed to identify genetic risk factors within the major histocompatibility complex for JIAU and evaluate their contribution for improving risk classification when combined with clinical risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data on single nucleotide polymorphisms, amino acids, and classical HLA alleles were available for 2,497 patients with JIA without uveitis and 579 patients with JIAU (female 2,060, male 1,015). Analysis was restricted to patients with inferred European ancestry. Forward conditional logistic regression identified genetic markers exceeding a Bonferroni\u2010corrected significance (6 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). Multivariable logistic regression estimated the effects of clinical and genetic risk factors, and a likelihood ratio test calculated the improvement in model fit when adding genetic factors. Uveitis risk classification performance of a model integrating genetic and clinical risk factors was estimated using area under the receiver operator characteristic curve and compared with a model of clinical risk factors alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three genetic risk factors were identified, mapping to\n                      <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                      ,\n                      <jats:italic>HLA\u2010DPB1<\/jats:italic>\n                      , and\n                      <jats:italic>HLA\u2010A<\/jats:italic>\n                      . These markers were statistically independent from clinical risk factors and significantly improved the fit of a model when included with clinical risk factors (\n                      <jats:italic>P<\/jats:italic>\n                      = 3.3 \u00d7 10\n                      <jats:sup>\u221223<\/jats:sup>\n                      ). The addition of genetic markers improved the classification of JIAU compared with a model of clinical risk factors alone (area under the curve 0.75 vs 0.71).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integration of a genetic and clinical risk prediction model outperforms a model based solely on clinical risk factors. Future JIAU risk prediction models should include genetic risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42955","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T04:19:11Z","timestamp":1721362751000},"page":"1789-1796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integration of Genetic and Clinical Risk Factors for Risk Classification of Uveitis in Patients With Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-0921","authenticated-orcid":false,"given":"Melissa","family":"Tordoff","sequence":"first","affiliation":[{"name":"The University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Smith","sequence":"additional","affiliation":[{"name":"The University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-162X","authenticated-orcid":false,"given":"Saskia","family":"Lawson\u2010Tovey","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Dick","sequence":"additional","affiliation":[{"name":"University of Bristol, Bristol, UCL Institute of Ophthalmology, London, and Moorfields Eye Hospital  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Beresford","sequence":"additional","affiliation":[{"name":"University of Liverpool and Alder Hey Children's NHS Foundation Trust Hospital  Liverpool United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athimalaipet V.","family":"Ramanan","sequence":"additional","affiliation":[{"name":"Bristol Royal Hospital for Children and University of Bristol  Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimme L.","family":"Hyrich","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Morris","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Eyre","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-1429","authenticated-orcid":false,"given":"Lucy R.","family":"Wedderburn","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, UCL Hospital and Great Ormond Street Hospital, and NIHR Biomedical Research Centre at Great Ormond Street Hospital  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bowes","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CLUSTER Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1139","article-title":"Prevalence and outcome of juvenile idiopathic arthritis\u2010associated uveitis and relation to articular disease","volume":"34","author":"Grassi A","year":"2007","journal-title":"J Rheumatol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.07.052"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40484"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.108322"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.20"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-019-00331-6"},{"issue":"2","key":"e_1_2_7_8_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_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23871"},{"key":"e_1_2_7_10_1","unstructured":"Royal College of Ophthalmologists 2006 Guidelines for screening for uveitis in juvenile idiopathic arthritis (JIA) produced jointly by BSPAR and the RCOphth 2006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1136\/annrheumdis-2018-213131","article-title":"Consensus\u2010based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative","volume":"77","author":"Constantin T","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.18295\/2075-0528.2797","article-title":"Challenges of childhood uveitis","volume":"9","author":"Abdwani R.","year":"2009","journal-title":"Sultan Qaboos Univ Med J"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/ijr.12.83"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa733"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/OARRR.S165916"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-016-0088-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/09273948.2013.815785"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210025"},{"key":"e_1_2_7_19_1","unstructured":"Biologics for Children with Rheumatic Diseases and British Society for Paediatric and Adolescent Rheumatology. Accessed August 11 2023.https:\/\/sites.manchester.ac.uk\/bcrdbspar\/"},{"key":"e_1_2_7_20_1","unstructured":"Childhood Arthritis Prospective Study. Accessed August 11 2023.http:\/\/www.caps-jia.org.uk\/"},{"key":"e_1_2_7_21_1","unstructured":"Childhood Arthritis Response to Medication Study.Great Ormond Street Hospital Charity. Accessed August 11 2023.https:\/\/www.gosh.nhs.uk\/wards\u2010and\u2010departments\/departments\/clinical\u2010specialties\/rheumatology\u2010information\u2010parents\u2010and\u2010visitors\/research\u2010and\u2010publications\u2010rheumatology\u2010department\/#:~:text=Our%20CHARMS%20study%20(Childhood%20Arthritis with%20a%20child%20with%20arthritis."},{"key":"e_1_2_7_22_1","unstructured":"United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium.http:\/\/www.cfgg.manchester.ac.uk\/research\/resources\/sample-collections\/"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218481"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr599"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx299"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064683"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42329"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/09273948.2013.791701"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27424"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40544"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27416"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S342717"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab246"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-eular.430"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42955","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:53:33Z","timestamp":1759956813000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":33,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/art.42955"],"URL":"https:\/\/doi.org\/10.1002\/art.42955","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]},"assertion":[{"value":"2023-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}