{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:49:46Z","timestamp":1791002986906,"version":"4.1.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001721","name":"Rijksuniversiteit Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007793","name":"Stiftelsen Kristian Gerhard Jebsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Celiac disease (CeD) is a complex T cell-mediated enteropathy induced by gluten. Although genome-wide association studies have identified numerous genomic regions associated with CeD, it is difficult to accurately pinpoint which genes in these loci are most likely to cause CeD. We used four different\n                    <jats:italic>in silico<\/jats:italic>\n                    approaches\u2014Mendelian randomization inverse variance weighting, COLOC, LD overlap, and DEPICT\u2014to integrate information gathered from a large transcriptomics dataset. This identified 118 prioritized genes across 50 CeD-associated regions. Co-expression and pathway analysis of these genes indicated an association with adaptive and innate cytokine signaling and T cell activation pathways. Fifty-one of these genes are targets of known drug compounds or likely druggable genes, suggesting that our methods can be used to pinpoint potential therapeutic targets. In addition, we detected 172 gene combinations that were affected by our CeD-prioritized genes in\n                    <jats:italic>trans<\/jats:italic>\n                    . Notably, 41 of these\n                    <jats:italic>trans<\/jats:italic>\n                    -mediated genes appear to be under control of one master regulator,\n                    <jats:italic>TRAF-type zinc finger domain containing 1<\/jats:italic>\n                    (\n                    <jats:italic>TRAFD1<\/jats:italic>\n                    ), and were found to be involved in interferon (IFN)\u03b3 signaling and MHC I antigen processing\/presentation. Finally, we performed\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments in a human monocytic cell line that validated the role of\n                    <jats:italic>TRAFD1<\/jats:italic>\n                    as an immune regulator acting in\n                    <jats:italic>trans<\/jats:italic>\n                    . Our strategy confirmed the role of adaptive immunity in CeD and revealed a genetic link between CeD and IFN\u03b3 signaling as well as with MHC I antigen processing, both major players of immune activation and CeD pathogenesis.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2020.562434","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T05:39:33Z","timestamp":1611553173000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Systematic Prioritization of Candidate Genes in Disease Loci Identifies TRAFD1 as a Master Regulator of IFN\u03b3 Signaling in Celiac Disease"],"prefix":"10.3389","volume":"11","author":[{"given":"Adriaan","family":"van der Graaf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Zorro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annique","family":"Claringbould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urmo","family":"V\u00f5sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Aguirre-Gamboa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joram","family":"Mooiweer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis","family":"Rica\u00f1o-Ponce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Borek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Kooy-Winkelaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Wang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lude","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebo","family":"Withoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cisca","family":"Wijmenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Sanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"BIOS Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00281-012-0316-x","article-title":"Intraepithelial lymphocytes in celiac disease immunopathology","volume":"34","author":"Abadie","year":"2012","journal-title":"Semin. 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