Identification of Susceptibility Modules and Genes for Cardiovascular Disease in Diabetic Patients Using WGCNA Analysis

OBJECTIVE: To identify susceptibility modules and genes for cardiovascular disease in diabetic patients using weighted gene coexpression network analysis (WGCNA). METHODS: The raw data of GSE13760 were downloaded from the Gene Expression Omnibus (GEO) website. Genes with a false discovery rate < 0.05 and a log2 fold change ≥ 0.5 were included in the analysis. WGCNA was used to build a gene coexpression network, screen important modules, and filter the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the genes in modules with clinical interest. Genes with a significance over 0.2 and a module membership over 0.8 were used as hub genes. Subsequently, we screened these hub genes in the published genome-wide SNP data of cardiovascular disease. The overlapped genes were defined as key genes. RESULTS: Fourteen gene coexpression modules were constructed via WGCNA analysis. Module greenyellow was mostly significantly correlated with diabetes. The GO analysis showed that genes in the module greenyellow were mainly enriched in extracellular matrix organization, extracellular exosome, and calcium ion binding. The KEGG analysis showed that the genes in the module greenyellow were mainly enriched in antigen processing and presentation, phagosome. Fifteen genes were identified as hub genes. Finally, HLA-DRB1, LRP1, and MMP2 were identified as key genes. CONCLUSION: This was the first study that used the WGCNA method to construct a coexpression network to explore diabetes-associated susceptibility modules and genes for cardiovascular disease. Our study identified a module and several key genes that acted as essential components in the etiology of diabetes-associated cardiovascular disease, which may enhance our fundamental knowledge of the molecular mechanisms underlying this disease.