{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:30:32Z","timestamp":1768509032622,"version":"3.49.0"},"posted":{"date-parts":[[2023,10,6]]},"group-title":"Genetics","reference-count":85,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,10,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Fine mapping and bioinformatic analysis of the\n                  <jats:italic>DDX6-CXCR5<\/jats:italic>\n                  genetic risk association in Sj\u00f6gren\u2019s Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer\/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on\n                  <jats:italic>DDX6<\/jats:italic>\n                  and\n                  <jats:italic>CXCR5<\/jats:italic>\n                  expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including\n                  <jats:italic>lnc-PHLDB1-1<\/jats:italic>\n                  . Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and\/or enhancer activities that regulate cell type-specific expression of\n                  <jats:italic>DDX6<\/jats:italic>\n                  ,\n                  <jats:italic>CXCR5<\/jats:italic>\n                  , and\n                  <jats:italic>lnc-PHLDB1-1<\/jats:italic>\n                  , among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.\n                <\/jats:p>","DOI":"10.1101\/2023.10.05.561076","type":"posted-content","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T08:40:52Z","timestamp":1696840852000},"source":"Crossref","is-referenced-by-count":0,"title":["Variants in the\n                  <i>DDX6-CXCR5<\/i>\n                  autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland"],"prefix":"10.64898","author":[{"given":"Mandi M.","family":"Wiley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhuwan","family":"Khatri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle 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