{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:47:47Z","timestamp":1788223667143,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01-AR-06060"],"award-info":[{"award-number":["R01-AR-06060"]}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Drs. Jiang and Zhu contributed equally to this work"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Juvenile idiopathic arthritis (JIA) is considered a complex disease in which the environment interacts with inherited genes to produce a phenotype that shows broad interindividual variability. Twenty\u2010four regions of genetic risk for JIA were identified in a recent genome\u2010wide association study (GWAS); however, as is typical of the results of GWAS, most of the regions of genetic risk (22 of 24) were in noncoding regions of the genome. This study was undertaken to identify functional elements (other than genes) that might be located within the regions of genetic risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used paired\u2010end RNA sequencing to identify noncoding RNAs (ncRNAs) located within 5 kb of disease\u2010associated single\u2010nucleotide polymorphisms (SNPs). In addition, we used chromatin immunoprecipitation (ChIP) followed by sequencing to identify epigenetic marks associated with enhancer function (H3K4me1 and H3K27ac) in human neutrophils to determine whether enhancer\u2010associated histone marks were enriched in the linkage disequilibrium blocks that encompassed the 22 SNPs identified in the GWAS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In human neutrophils, we identified H3K4me1 and\/or H3K27ac marks in 15 of the 22 regions previously identified as risk loci for JIA. In CD4+ T cells, 18 regions had H3K4me1 and\/or H3K27ac marks. In addition, we identified ncRNA transcripts at the rs4705862 and rs6894249 loci in human neutrophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Much of the genetic risk for JIA lies within or adjacent to regions of neutrophil and CD4+ T cell genomes that carry epigenetic marks associated with enhancer function and\/or ncRNA transcripts. These findings are consistent with the hypothesis that JIA is fundamentally a disorder of gene regulation that includes both the innate and the adaptive immune system. Elucidating the specific roles of these noncoding elements within leukocyte genomes will be critical to our understanding of JIA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39135","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T15:35:24Z","timestamp":1427902524000},"page":"1966-1977","source":"Crossref","is-referenced-by-count":44,"title":["Disease\u2010Associated Single\u2010Nucleotide Polymorphisms From Noncoding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells"],"prefix":"10.1002","volume":"67","author":[{"given":"Kaiyu","family":"Jiang","sequence":"first","affiliation":[{"name":"University at Buffalo Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Zhu","sequence":"additional","affiliation":[{"name":"University at Buffalo Buffalo New 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