{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T05:30:28Z","timestamp":1780723828115,"version":"3.54.1"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify the genetic variants that affect gene expression (expression quantitative trait loci [eQTLs]) in systemic sclerosis (SSc) and to investigate their role in the pathogenesis of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed an eQTL analysis using whole\u2010blood sequencing data from 333 SSc patients and 524 controls and integrated them with SSc genome\u2010wide association study (GWAS) data. We integrated our findings from expression modeling, differential expression analysis, and transcription factor binding site enrichment with key clinical features of SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected 49,123 validated <jats:italic>cis<\/jats:italic>\u2010eQTLs from 4,539 SSc\u2010associated single\u2010nucleotide polymorphisms (SNPs) (<jats:italic>P<\/jats:italic><jats:sub>GWAS<\/jats:sub> &lt; 10<jats:sup>\u22125<\/jats:sup>). A total of 1,436 genes were within 1 Mb of the 4,539 SSc\u2010associated SNPs. Of those 1,436 genes, 565 were detected as having \u22651 eQTL with an SSc\u2010associated SNP. We developed a strategy to prioritize disease\u2010associated genes based on their expression variance explained by SSc eQTLs (r<jats:sup>2<\/jats:sup> &gt; 0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in the blood cells, skin, or lung tissue of SSc patients. Transcription factor binding site analysis revealed enriched motifs of 24 transcription factors (5%) among SSc eQTLs, 5 of which were found to be differentially regulated in the blood cells (<jats:italic>ELF1<\/jats:italic> and <jats:italic>MGA<\/jats:italic>), skin (<jats:italic>KLF4<\/jats:italic> and <jats:italic>ID4<\/jats:italic>), and lungs (<jats:italic>TBX4<\/jats:italic>) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune\u2010mediated diseases, of which only 3 have been tested in clinical trials in patients with SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of the present study indicate a new layer to the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41657","type":"journal-article","created":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T05:47:33Z","timestamp":1610862453000},"page":"1288-1300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Expression Quantitative Trait Locus Analysis in Systemic Sclerosis Identifies New Candidate Genes Associated With Multiple Aspects of Disease Pathology"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-4514","authenticated-orcid":false,"given":"Martin","family":"Kerick","sequence":"first","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra CSIC  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-7081","authenticated-orcid":false,"given":"David","family":"Gonz\u00e1lez\u2010Serna","sequence":"additional","affiliation":[{"name":"Institute of Parasitology and Biomedicine L\u00f3pez\u2010Neyra CSIC  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Carnero\u2010Montoro","sequence":"additional","affiliation":[{"name":"Pfizer\u2013University of Granada\u2013Junta de Andaluc\u00eda Centre for Genomics and Oncological Research  Granada 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