Protein-protein Interaction Network Analysis Of Genes Related To Obesity

Obesity is a chronic metabolic disease determined by a combination of genetic and environmental factors. With the rapid growth of prevalence and incidence of obesity throughout the world, more and more people are deeply suffered from obesity and its complications. Human genome-wide genetic studies and transcriptomic studies on adipocytes have played important roles in identification of candidate susceptibility genes for obesity. However, traditional analysis methods mainly focus on the effect of certain gene or certain DNA variant individually, so the effect of gene-gene interaction on polygenic diseases can’t be detected effectively. In this study, to identify new genes and network modules that play important roles in obesity and adipogenesis, we performed protein-protein network analysis for one genome-wide association study (GWAS) data set and three transcriptomic profiling studies of adipogenesis.This study includes two parts:①We conducted meta-analysis of three gene expression profiling studies followed by a protein-protein interaction(PPI) network analysis on differentially expressed genes (DEGs);②We performed PPI network analysis for genes identified from gene-based genome-wide association study in a Han Chinese population.We firstly performed a meta-analysis of three gene expression profiling studies on human adipogenesis (GSE28628、 GSE37836、 GSE39342) to get reliable DEGs during adipogenesis. A total of1505and304DEGs (Meta P＜0.01, fold change≥2or≤0.5and P＜0.05at least in two individual studies) were identified for the early and late adipogenesis. The genes of greatest significance are HNT (P=1.41×10-14) and LETMD1(P=1.65×10-11), respectively. In PPI network analysis of these DEGs, we found that these genes are interact extensively. The biggest subnetwork of DEGs during early adipogenesis consists of699genes with7statistically significant network modules (P<0.05). The biggest subnetwork of DEGs during late adipogenesis consisted of51genes with6statistically significant network modules (P<0.05). Topology analysis of the network suggested series of network hub genes, such as CDK2(Degree=95, Betweenness=9177.05), HDACl (Degree=62, Betweenness=4431.97), BRCA1(Degree=47, Betweenness=2084.01) in the early adipogenesis network; EGR1(Degree=9, Betweenness=14), IL7R (Degree=6, Betweenness=4), PPARG (Degree=6, Betweenness=0) in the late adipogenesis network。Through gene-based GWAS on a Han Chinese population, we identified280genes associated with obesity, with CD55being the most significant one (P=1.10×10-5). In the PPI network of these280genes, the biggest subnetwork consists of30genes. Some important hub genes of this subnetwork are PCNA (Degree=7, Betweenness=0) CUL4A (Degree=7, Betweenness=0), CREBBP (Degree=6, Betweenness=8)。The genes, network modules and interaction relationships identified in this study provided new insights for the study of the pathology of obesity. Further functional studies of these genes and modules will be helpful for revealing the importance and mechanisms of these genes/modules on obesity and providing a potential target for the diagnosis and treatment of obesity.