Abstract
BackgroundAtrial fibrillation (AF) is at least partially heritable, affecting 2–3% of the population in Europe and the USA. However, a substantial proportion of heritability is still lacking. In the present study, we aim to identify potential crucial genes associated with AF through bioinformatic analyses of public datasets.MethodsMicroarray data sets of GSE115574, GSE31821, GSE79768, GSE41177 and GSE14975 from the Gene Expression Omnibus (GEO) database were retrieved. After merging all microarray data and adjusting batch effect, differentially expressed genes (DEGs) were identified. Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, Gene Set Enrichment Analysis (GSEA), Reactome Pathway Database and Disease Ontology (DO) were carried out. Protein-protein interaction (PPI) network was constructed using the STRING database. Combined with aforementioned significant bioinformatics information, potential crucial genes were subsequently selected. The comparative toxicogenomics database (CTD) was used to explore the interaction between potential crucial genes and AF.ResultWe identified 27 of DEGs with gene expression fold change (FC) ≥ 1.5 or ≤ 2/3 (|log2 FC| ≥ 0.58) and 5 with FC ≥ 2 or ≤ 0.5 (|log2 FC| ≥ 1) of AF patients compared with sinus rhythm controls. The most significantly enriched pathway was regulation of insulin-like growth factor transport and uptake by insulin-like growth factor binding proteins. IGFBP2, C1orf105, FHL2, CHGB, ATP1B4, IGFBP3, SLC26A9, CXCR4 and HTR2B were considered the potential crucial genes. CTD showed CXCR4, IGFBP2, IGFBP3 and FHL2 had higher scores with AF.ConclusionsThe 9 potential crucial genes, especially CXCR4, IGFBP2, IGFBP3 and FHL2, may be associated with risk of AF. Our study provided new insights of AF into genetics, molecular pathogenesis and new therapeutic targets.
Highlights
Atrial fibrillation (AF) is at least partially heritable, affecting 2–3% of the population in Europe and the USA
Twentyseven of differentially expressed genes (DEGs) with |log2 fold change (FC)| ≥ 0.58 in left atrial appendage (LAA) samples of AF patients compared with sinus rhythm (SR) was identified, including 19 up-regulated genes and 8 down-regulated genes (Supplementary Table 1)
Our study revealed that the IGFBP2 expression level was up-regulated in AF samples compared to SR samples
Summary
Atrial fibrillation (AF) is at least partially heritable, affecting 2–3% of the population in Europe and the USA. A substantial proportion of heritability is still lacking. We aim to identify potential crucial genes associated with AF through bioinformatic analyses of public datasets. Only a small proportion of exposed individuals eventually developed AF, suggesting that a strong genetic component might be a risk factor contributing to the susceptibility of AF. In 2018, a preliminary genome-wide association study meta-analysis including over 93,000 AF cases and more than 1 million referents identified at least 134 genetic loci significantly associated with risk of AF [9]. One potential interpretation is that unidentified genes may partially contribute to the missing heritability. There are still many related genes to be identified, which will help us better understand the pathogenesis of AF and facilitate the discovery of novel diagnostic biomarkers or therapeutic target
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
