{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dey KK"],"funding":["NHGRI NIH HHS"],"pagination":["100145"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9306342"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(7)"],"pubmed_abstract":["We assess contributions to autoimmune disease of genes whose regulation is driven by enhancer regions (enhancer-related) and genes that regulate other genes in <i>trans</i> (candidate master-regulator). We link these genes to SNPs using several SNP-to-gene (S2G) strategies and apply heritability analyses to draw three conclusions about 11 autoimmune/blood-related diseases/traits. First, several characterizations of enhancer-related genes using functional genomics data are informative for autoimmune disease heritability after conditioning on a broad set of regulatory annotations. Second, candidate master-regulator genes defined using <i>trans</i>-eQTL in blood are also conditionally informative for autoimmune disease heritability. Third, integrating enhancer-related and master-regulator gene sets with protein-protein interaction (PPI) network information magnified their disease signal. The resulting PPI-enhancer gene score produced >2-fold stronger heritability signal and >2-fold stronger enrichment for drug targets, compared with the recently proposed enhancer domain score. In each case, functionally informed S2G strategies produced 4.1- to 13-fold stronger disease signals than conventional window-based strategies."],"journal":["Cell genomics"],"pubmed_title":["SNP-to-gene linking strategies reveal contributions of enhancer-related and candidate master-regulator genes to autoimmune disease."],"pmcid":["PMC9306342"],"funding_grant_id":["R00 HG009917","K99 HG012203","R35 HG011324"],"pubmed_authors":["Price AL","van de Geijn B","Nasser J","Kim SS","Dey KK","Gazal S","Engreitz JM"],"additional_accession":[]},"is_claimable":false,"name":"SNP-to-gene linking strategies reveal contributions of enhancer-related and candidate master-regulator genes to autoimmune disease.","description":"We assess contributions to autoimmune disease of genes whose regulation is driven by enhancer regions (enhancer-related) and genes that regulate other genes in <i>trans</i> (candidate master-regulator). We link these genes to SNPs using several SNP-to-gene (S2G) strategies and apply heritability analyses to draw three conclusions about 11 autoimmune/blood-related diseases/traits. First, several characterizations of enhancer-related genes using functional genomics data are informative for autoimmune disease heritability after conditioning on a broad set of regulatory annotations. Second, candidate master-regulator genes defined using <i>trans</i>-eQTL in blood are also conditionally informative for autoimmune disease heritability. Third, integrating enhancer-related and master-regulator gene sets with protein-protein interaction (PPI) network information magnified their disease signal. The resulting PPI-enhancer gene score produced >2-fold stronger heritability signal and >2-fold stronger enrichment for drug targets, compared with the recently proposed enhancer domain score. In each case, functionally informed S2G strategies produced 4.1- to 13-fold stronger disease signals than conventional window-based strategies.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2024-11-09T16:10:30.159Z","creation":"2024-11-09T16:10:30.159Z"},"accession":"S-EPMC9306342","cross_references":{"pubmed":["35873673"],"doi":["10.1016/j.xgen.2022.100145"]}}