PDE3A and GSK3B as Atrial Fibrillation Susceptibility Genes in the Chinese Population via Bioinformatics and Genome-Wide Association Analysis

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with uncovered genetic etiology and pathogenesis. We aimed to screen out AF susceptibility genes with potential pathogenesis significance in the Chinese population. Methods: Differentially expressed genes (DEGs) were screened by the Limma package in three GEO data sets of atrial tissue. AF-related genes were identified by combination of DEGs and public GWAS susceptibility genes. Potential drug target genes were selected using the DrugBank, STITCH and TCMSP databases. Pathway enrichment analyses of AF-related genes were performed using the databases GO and KEGG databases. The pathway gene network was visualized by Cytoscape software to identify gene–gene interactions and hub genes. GWAS analysis of 110 cases of AF and 1201 controls was carried out through a genome-wide efficient mixed model in the Fangshan population to verify the results of bioinformatic analysis. Results: A total of 3173 DEGs were identified, 57 of which were found to be significantly associated with of AF in public GWAS results. A total of 75 AF-related genes were found to be potential therapeutic targets. Pathway enrichment analysis selected 79 significant pathways and classified them into 7 major pathway networks. A total of 35 hub genes were selected from the pathway networks. GWAS analysis identified 126 AF-associated loci. PDE3A and GSK3B were found to be overlapping genes between bioinformatic analysis and GWAS analysis. Conclusions: We screened out several pivotal genes and pathways involved in AF pathogenesis. Among them, PDE3A and GSK3B were significantly associated with the risk of AF in the Chinese population. Our study provided new insights into the mechanisms of action of AF.

Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning

“…For example, Zhang et al have shown that CXCR4 and TYROBP are involved in the occurrence of AF, and the mechanism of action may be related to the activation of inflammatory pathways 19 . The PDE3A and GSK3B genes, as identified by Zhou et al, exhibit a significant association with the risk of AF in the Chinese population, providing a new theoretical basis for studying the pathogenesis of AF 20 . Based on WGCNA and machine learning techniques, Zhu et al found that NPPA , OMD , and PRELP could be used as diagnostic biomarkers for DCM combined with HF 21 .…”

“… 19 The PDE3A and GSK3B genes, as identified by Zhou et al, exhibit a significant association with the risk of AF in the Chinese population, providing a new theoretical basis for studying the pathogenesis of AF. 20 Based on WGCNA and machine learning techniques, Zhu et al found that NPPA , OMD , and PRELP could be used as diagnostic biomarkers for DCM combined with HF. 21 These findings may help us better understand the pathogenesis of AF and HF, as well as facilitate the discovery of new diagnostic biomarkers or therapeutic targets.…”