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dc.contributor.authorWang, Qiang
dc.contributor.authorMartínez-Bonet, Marta
dc.contributor.authorKim, Taehyeung
dc.contributor.authorSparks, Jeffrey A.
dc.contributor.authorIshigaki, Kazuyoshi
dc.contributor.authorChen, Xiaoting
dc.contributor.authorSudman, Marc
dc.contributor.authorAguiar, Vitor
dc.contributor.authorSim, Sangwan
dc.contributor.authorHernandez, Marcos Chiñas
dc.contributor.authorChiu, Darren J.
dc.contributor.authorWactor, Alexandra
dc.contributor.authorWauford, Brian
dc.contributor.authorMarion, Miranda C.
dc.contributor.authorGutierrez-Arcelus, Maria
dc.contributor.authorBowes, John
dc.contributor.authorEyre, Stephen
dc.contributor.authorNordal, Ellen Berit
dc.contributor.authorPrahalad, Sampath
dc.contributor.authorRygg, Marite
dc.contributor.authorVidem, Vibeke
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorWeirauch, Matthew T.
dc.contributor.authorLangefeld, Carl D.
dc.contributor.authorThompson, Susan D.
dc.contributor.authorNigrovic, Peter A.
dc.date.accessioned2024-01-03T13:20:18Z
dc.date.available2024-01-03T13:20:18Z
dc.date.issued2023-10-16
dc.description.abstractTRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using Immunochip data from 3,939 patients with juvenile idiopathic arthritis (JIA) and 14,412 control individuals, we identified 132 plausible common non-coding variants, reduced serially by single-nucleotide polymorphism sequencing (SNP-seq), electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron of TRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-related antigen 2 (FRA2), encoded by FOSL2, resulting in reduced TRAF1 expression and enhanced tumor necrosis factor (TNF) production. Conditioning on this JIA variant eliminated attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding functional variant drives risk of inflammatory arthritis in children and adults.en_US
dc.identifier.citationWang, Martínez-Bonet, Kim, Sparks, Ishigaki, Chen, Sudman, Aguiar, Sim, Hernandez, Chiu, Wactor, Wauford, Marion, Gutierrez-Arcelus, Bowes, Eyre, Nordal, Prahalad, Rygg, Videm, Raychaudhuri, Weirauch, Langefeld, Thompson, Nigrovic. Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant. Cell Genomics. 2023;3(11)en_US
dc.identifier.cristinIDFRIDAID 2200788
dc.identifier.doi10.1016/j.xgen.2023.100420
dc.identifier.issn2666-979X
dc.identifier.urihttps://hdl.handle.net/10037/32301
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalCell Genomics
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en_US
dc.titleIdentification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding varianten_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)