Integrated bioinformatics analysis of aberrantly-methylated differentially-expressed genes and pathways in age-related macular degeneration

Abstract

Background: Age-related macular degeneration (AMD) represents the leading cause of visual impairment in the aging population. The goal of this study was to identify aberrantly-methylated, differentially-expressed genes (MDEGs) in AMD and explore the involved pathways via integrated bioinformatics analysis.Methods: Data from expression profile GSE29801 and methylation profile GSE102952 were obtained from the Gene Expression Omnibus database. We analyzed differentially-methylated genes and differentially-expressed genes using R software. Functional enrichment and protein-protein interaction (PPI) network analysis were performed using the R package and Search Tool for the Retrieval of Interacting Genes online database. Hub genes were identified using Cytoscape. Results:In total, 827 and 592 genes showed high and low expression, respectively, in GSE29801; 4117 hyper-methylated genes and 511 hypo-methylated genes were detected in GSE102952. Based on overlap, we categorized 153 genes as hyper-methylated, low-expression genes (Hyper-LGs) and 24 genes as hypo-methylated, high-expression genes (Hypo-HGs). Four Hyper-LGs (CKB, PPP3CA, TGFB2, SOCS2) overlapped with AMD risk genes in the Public Health Genomics and Precision Health Knowledge Base. KEGG pathway enrichment analysis indicated that Hypo-HGs were enriched in the calcium signaling pathway, whereas Hyper-LGs were enriched in sphingolipid metabolism. In GO analysis, Hypo-HGs were enriched in fibroblast migration, membrane raft, and coenzyme binding, among others. Hyper-LGs were enriched in mRNA transport, nuclear speck, and DNA binding, among others. In PPI network analysis, 23 nodes and two edges were established from Hypo-HGs, and 151 nodes and 73 edges were established from Hyper-LGs. Hub genes (DHX9, MAPT, PAX6) showed the greatest overlap. Conclusion: This study revealed potentially aberrantly MDEGs and pathways in AMD, which might improve the understanding of this disease. Background Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries, particularly in those over 55 years of age. Worldwide, this condition accounts for 7% of accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The written consent was not applicable. . The sponsor or funding organization had no role in the design or conduct of this research. Authors' contributions: YS conceived and coordinated the project, complied the figures and the tables and wrote the manuscript. ML performed statistical analysis of all data, compiled functional enrichment analysis and protein-protein interaction network analysis. KL, SPZ and XYX helped to coordinate data analysis and screened the hub genes. WG, QZ, PL and NW helped with data curation and searching information in different databases. FY sourced the database and performed statistical analysis of all data. XX conceived and directed the project and wrote the manuscript. All auth...