{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:45:35Z","timestamp":1791859535116,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc\u2013RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc\u2013RA loci through an interdisease meta\u2013genome\u2010wide association (meta\u2010GWAS) strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was designed as a meta\u2010analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same\u2010direction and opposite\u2010direction allelic effects. The top single\u2010nucleotide polymorphisms were followed up in independent SSc and RA case\u2013control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This cross\u2010disease meta\u2010analysis of the GWAS data sets identified several loci with nominal association signals (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20095 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) that also showed evidence of association in the disease\u2010specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow\u2010up analyses of the putatively new SSc\u2013RA loci identified\n                      <jats:italic>IRF4<\/jats:italic>\n                      as a shared risk factor for these 2 diseases (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>combined<\/jats:sub>\n                      \u2009=\u20093.29 \u00d7 10\n                      <jats:sup>\u221212<\/jats:sup>\n                      ). Analysis of the biologic relevance of the known SSc\u2013RA shared loci identified the type I interferon and interleukin\u201012 signaling pathways as the main common etiologic factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified a novel shared locus,\n                      <jats:italic>IRF4<\/jats:italic>\n                      , for the risk of SSc and RA, and highlighted the usefulness of a cross\u2010disease GWAS meta\u2010analysis strategy in the identification of common risk loci.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39730","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T20:22:49Z","timestamp":1461615769000},"page":"2338-2344","source":"Crossref","is-referenced-by-count":51,"title":["Brief Report:\n                    <i>IRF4<\/i>\n                    Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross\u2010Disease Meta\u2010Analysis of Genome\u2010Wide Association Studies"],"prefix":"10.1002","volume":"68","author":[{"given":"Elena","family":"L\u00f3pez\u2010Isac","sequence":"first","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra CSIC Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u2010Ezequiel","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra CSIC Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen P.","family":"Sime\u00f3n","sequence":"additional","affiliation":[{"name":"Valle de Hebr\u00f3n Hospital Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Carreira","sequence":"additional","affiliation":[{"name":"12 de Octubre University Hospital Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norberto","family":"Ortego\u2010Centeno","sequence":"additional","affiliation":[{"name":"Clinic University Hospital Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayka","family":"Freire","sequence":"additional","affiliation":[{"name":"Complexo Hospitalario Universitario de Vigo Vigo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Narv\u00e1ez","sequence":"additional","affiliation":[{"name":"Hospital Universitari de Bellvitge Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Alegre\u2010Sancho","sequence":"additional","affiliation":[{"name":"Hospital Universitari Doctor Peset Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Spanish Scleroderma Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Fern\u00e1ndez\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Balsa","sequence":"additional","affiliation":[{"name":"Hospital Universitario La Paz, Instituto de Investigaci\u00f3n Sanitaria La Paz Madrid 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W.","family":"Distler","sequence":"additional","affiliation":[{"name":"University of Erlangen\u2013Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Riekemasten","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette H.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeska","family":"de Vries\u2010Bouwstra","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Magro\u2010Checa","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre E.","family":"Voskuyl","sequence":"additional","affiliation":[{"name":"VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelon C.","family":"Vonk","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8yvind","family":"Molberg","sequence":"additional","affiliation":[{"name":"Oslo University Hospital Rikshospitalet and Institute of Clinical Medicine, University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Merriman","sequence":"additional","affiliation":[{"name":"University of Otago  Otago New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Hesselstrand","sequence":"additional","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Nordin","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Herrick","sequence":"additional","affiliation":[{"name":"University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Eyre","sequence":"additional","affiliation":[{"name":"University of Manchester, Manchester Academic Health Science Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby P. 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