In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes.

Type 1 diabetes (T1D) is a multifactorial, polygenic complex autoimmune disease damaging pancreatic islet β cells. Numerous genes linked to T1D have been discovered through genetical studies, GWAS and polymorphisms. Most genetical studies focused on independent genes while others overemphasized on SNPs. Here, a collective analysis of documented T1D-associated genes was performed using bioinformatics tools. Enriched biological pathways, functions, enrichment clustering, networks and interactomes were analysed. Besides, meta-analyses of T1D-associated genes and T1D-related genes from SNPs were investigated to find common genes, pathways, enrichment and interrelationships. Notable enriched pathways comprised of cytokine-mediated signalling, cytokine production, interferon gamma production, myeloid leukocyte activation, activation of immune response, lymphocyte activation, adaptive immune response, Th17 cell differentiation etc. Enrichment analysis of T1D-associated genes emphasized the role of immune-linked machineries in metabolism, disease progression and aetiology of type 1 diabetes. Interactome analysis revealed overrepresentation of T1D-associated genes compared with T1D-related genes from SNPs. MCODE components highlighted the significance of pathways linked to vitamin D metabolism, signalling by interleukins, toll-like receptors, chemokines, PD-1, NOTCH, antigen processes etc. About 153 genes from MCODE complexes representing enriched pathways of T1D-associated genes and T1D-related genes from SNPs play a crucial role and may be important for further investigations. The information may be valuable for designing precision medicine-based therapeutics.