Influence Of Type 2 Diabetes GWAS Associated SNPs On MiRNA-mRNA Interaction

Type 2 diabetes (T2D) is a complex disease which is influenced by both genetic and environmental factors, with a heritability estimate of 80%. GWAS becomes a main method to search for susceptibility genes of common diseases in the genome era. To date, a total of 53 T2D GWAS have reported 334 susceptibility genes and 324 SNPs (p <1×10-5). Future challenge is to elucidate functional mechanisms through which these GWAS associated loci modulate T2D disease risk. One of mechanisms is that SNPs regulate gene expression by affecting the interaction of miRNA-mRNA. Aim of this study is to identify GWAS T2D-associated SNPs that could influence miRNA-mRNA interaction through combination of computational and experimental approaches.GWAS T2D-associated SNPs are collected from the NCBI and HuGE Navigator. SNPs which were in strong linkage disequilibrium (LD) with GWAS T2D-associated SNPs were searched via HapMap Website. Target Scan, miRWalk, miRWalk, miRanda, Diana-microT and miRDB are used to analyze the interaction between genes and miRNA. miRNASNP, MirSNP, mrSNP and SNPinfo are employed to predict the influence of a 3’UTR SNP on miRNA binding. Positive prediction results are further elevated by dual-luciferase reporter gene system.We predicted miRNAs targeting T2D GWAS-associated hub genes. Thirty T2D GWAS-associated SNPs potentially affect 128 pairs of miRNA-mRNA interactions. We successfully validated allelic expression imbalance of rs11558471; however we are unable to validate effectt of rs6426514, rs11558471, rs2466293 and rs113040697 on miRNA-mRNA interaction by dual-luciferase reporter gene system. Our results highlight the limitation of computational predictions and importance of combining computational and experimental approaches.