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However, most of the genes associated with the disease are still unknown because associated variants affect mostly noncoding intergenic elements of the genome. We used functional genomics to translate the genetic findings into a better understanding of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Promoter capture Hi\u2010C and RNA\u2010sequencing experiments were performed in CD4+ T cells and CD14+ monocytes from 10 SSc patients and 5 healthy controls to link SSc\u2010associated variants with their target genes, followed by differential expression and differential interaction analyses between cell types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We linked SSc\u2010associated loci to 39 new potential target genes and confirmed 7 previously known SSc\u2010associated genes. We highlight novel causal genes, such as\n                      <jats:italic>CXCR5,<\/jats:italic>\n                      as the most probable candidate gene for the\n                      <jats:italic>DDX6<\/jats:italic>\n                      locus. Some previously known SSc\u2010associated genes, such as\n                      <jats:italic>IRF8, STAT4<\/jats:italic>\n                      , and\n                      <jats:italic>CD247<\/jats:italic>\n                      , showed cell type\u2013specific interactions. We also identified 15 potential drug targets already in use in other similar immune\u2010mediated diseases that could be repurposed for SSc treatment. Furthermore, we observed that interactions were directly correlated with the expression of important genes implicated in cell type\u2013specific pathways and found evidence that chromatin conformation is associated with genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study revealed potential causal genes for SSc\u2010associated loci, some of them acting in a cell type\u2013specific manner, suggesting novel biologic mechanisms that might mediate SSc pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42396","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T04:39:50Z","timestamp":1666672790000},"page":"1007-1020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification of Mechanisms by Which Genetic Susceptibility Loci Influence Systemic Sclerosis Risk Using Functional Genomics in Primary T Cells and Monocytes"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-7081","authenticated-orcid":false,"given":"David","family":"Gonz\u00e1lez\u2010Serna","sequence":"first","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC)  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenfu","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Musculoskeletal and Dermatological Sciences, Centre for Genetics and Genomics Versus Arthritis, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kerick","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra, Consejo Superior de Investigaciones Cient\u00edficas (IPBLN\u2010CSIC)  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Hankinson","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Musculoskeletal and Dermatological Sciences, Centre for Genetics and Genomics Versus Arthritis, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"McGovern","sequence":"additional","affiliation":[{"name":"Division of Musculoskeletal and Dermatological 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