Annotation of Type 1 Diabetes Functional Variants Through RegulomeDB

Abstract

Type 1 diabetes is an autoimmune disorder with multiple genes involved in its pathogenesis. To understand the regulatory role of the single nucleotide polymorphisms (SNPs) associated with these genes, functional annotation of SNPs associated with Type 1 Diabetes (T1D) and their proxy SNPs was performed. For this study, 70 target SNPs were selected on the bases of their significant association with Type 1 Diabetes (p-value < 5E−08) in different population taken from five previous studies. Using SNAP web portal SNPs (proxy SNPs) that were in Linkage Disequilibrium (LD) (r2 ≥ 0.08) with 70 reported target SNPs were searched. All the target and proxy SNPs were analyzed for potential regulatory functions using RegulomeDB database. RegulomeDB is a useful resource to assess the functional nature of implicated SNPs. Out of the total 1612 SNPs only 187 SNPs exhibited potential regulatory functions by scoring “less than 3” in RegulomeDB whereas 124 out of them scored “1” indicating its highly significant role. From these 187 SNPs with suggested regulatory functions, only 13 were the reported T1D associated genome-wide significant SNPs which are IL27/rs4788084 (score = 1a), CENPW/rs9388489 (score = 1a), HLA/rs9272346 (score = 1b), CD69/rs4763879 (score = 1d), CLEC16A/rs12708716 (score = 1f), ERBB3/rs2292239 (score = 1f), PRKCQ/rs11258747 (score = 1f), HLA/rs9268645 (score = 1f), intergenic/rs2165738 (score = 1f), RAB5B/rs11171710 (score = 1f), CTSH/rs3825932 (score = 1f), IL10/rs3024505 (score = 2b), PTPN22/rs2476601 (score = 2b). Remaining 175 SNPs were in LD with the 70 reported GWAS SNPs. Hence, regulatory role of the Type 1 Diabetes associated SNPs was revealed using RegulomeDB.