Open AccessComputational analyses of type 2 diabetes‐associated loci identified by genome‐wide association studies
Author(s) -
Cheng Mengrong,
Liu Xinhong,
Yang Mei,
Han Lanchun,
Xu Aimin,
Huang Qingyang
Publication year - 2017
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12421
Subject(s) - genome wide association study , tcf7l2 , single nucleotide polymorphism , genetics , biology , computational biology , genetic association , gene , bioinformatics , genotype
Background Genome‐wide association studies (GWAS) of type 2 diabetes (T2D) have discovered a number of loci that contribute to susceptibility to the disease. Future challenges include elucidation of functional mechanisms through which these GWAS‐identified loci modulate T2D disease risk. The aim of the present study was to comprehensively characterize T2D associated single nucleotide polymorphisms (SNPs) and genes through computational approaches. Methods Computational biology approaches used in the present study included comparative genomic analyses and functional annotation using GWAS3D and RegulomeDB, investigation of the effects of T2D‐associated SNPs on miRNA binding and protein phosphorylation, and gene ontology, pathway enrichment, protein–protein interaction (PPI) networks and functional module analysis of T2D‐associated genes from previously published GWAS. Results Computational analysis identified a number of T2D GWAS‐associated SNPs that were located at protein binding sites, including CCCTC‐binding factor (CTCF), E1A binding protein p300 (EP300), hepatocyte nuclear factor 4alpha (HNF4A), transcription factor 7 like 2 (TCF7L2), forkhead box A1 (FOXA1) and A2 (FOXA2), and potentially affected the binding of miRNAs and protein phosphorylation. Pathway enrichment analysis confirmed two well‐known maturity onset diabetes of the young and T2D pathways, whereas PPI network analysis identified highly interconnected “hub” genes, such as TCF7L2 , melatonin receptor 1B ( MTNR1B ), and solute carrier family 30 (zinc transporter), member 8 ( SLC30A8 ), that created two tight subnetworks. Conclusions The results provide objectives and clues for future experimental studies and further insights into the molecular pathogenesis of T2D.