Supporting data for: Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines

<strong>SUMMARY</strong> We combined functional genomics and human genetics to investigate processes that affect type 1 diabetes (T1D) risk by mediating beta-cell survival in response to proinflammatory cytokines. We mapped 38,931 cytokine-responsive candidate <em>cis-</em>regulatory elements (cCREs) in beta-cells using ATAC-seq and snATAC-seq and linked them to target genes using co-accessibility and HiChIP. Using a genome-wide CRISPR screen in EndoC-βH1 cells we identified 867 genes affecting cytokine-induced survival, and genes promoting survival and up-regulated in cytokines were enriched at T1D risk loci. Using SNP-SELEX, we identified 2,229 variants in cytokine-responsive cCREs altering transcription factor (TF) binding, and variants altering binding of TFs regulating stress, inflammation and apoptosis were enriched for T1D risk. At the 16p13 locus, a fine-mapped T1D variant altering TF binding in a cytokine-induced cCRE interacted with <em>SOCS1</em>, which promoted survival in cytokine exposure. Our findings reveal processes and genes acting in beta-cells during inflammation that modulate T1D risk. Raw data deposited at GEO, accessions GSE205853 and GSE118725.