{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:55:37Z","timestamp":1791305737003,"version":"4.3.1"},"posted":{"date-parts":[[2026,10,1]]},"group-title":"Genomics","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["5U24DK104162-12"],"award-info":[{"award-number":["5U24DK104162-12"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U24DK098085"],"award-info":[{"award-number":["U24DK098085"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK132651"],"award-info":[{"award-number":["R01DK132651"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK143607"],"award-info":[{"award-number":["R01DK143607"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Type 1 diabetes (T1D) is a complex autoimmune disease characterized by the destruction of insulin-producing pancreatic \u03b2 cells. Both genetic susceptibility and epigenetic dysregulation contribute to T1D risk. Recent studies have reported \u03b2-cell dysfunction before disease onset, suggesting that \u03b2-cell-intrinsic mechanisms contribute to pathogenesis. However, the mechanistic link between disease-associated variants and \u03b2-cell dysfunction remains poorly understood. We hypothesized that a subset of T1D-associated variants directly influences cell type-specific candidate cis-regulatory elements (cCREs) by disrupting transcription factor (TF) binding and altering gene expression. To define cell type-specific cCREs in human islets, we integrated publicly available epigenomic datasets, including bulk histone modification profiles and single-cell multiomic data from human pancreatic islets. We combined these data with T1D genome-wide association study (GWAS) variants to identify disease-associated SNPs located within enhancer regions. Using multiomic datasets from PANC-DB, we characterized cell type-specific chromatin accessibility in nondiabetic and T1D islets and identified regulatory regions that may control gene expression in \u03b2 cells and other islet cell types. We then applied ChromBPNet, a deep learning model that predicts base-pair-resolution chromatin accessibility from scATAC-seq data, to evaluate how specific variants may alter local regulatory activity. In parallel, we used TF footprinting to nominate TFs likely to bind these variant-containing regions. These analyses identified several T1D-associated SNPs predicted to alter chromatin accessibility at candidate TF binding sites, suggesting mechanisms by which noncoding variants may contribute to \u03b2-cell dysfunction and T1D susceptibility. Our findings link T1D-associated variants to cell type-specific enhancer activity and regulatory pathways and provide candidates for future mechanistic studies.<\/jats:p>","DOI":"10.64898\/2026.09.25.753922","type":"posted-content","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:15:22Z","timestamp":1790903722000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic risk and inflammatory signaling converge on cell type-specific regulatory programs in type 1 diabetes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-0170","authenticated-orcid":false,"given":"Liu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Scottsdale, AZ, 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