Identification of Common Hub Genes in COVID-19 and Comorbidities: Insights into Shared Molecular Pathways and Disease Severity

Identification of Common Hub Genes in COVID-19 and Comorbidities: Insights into Shared Molecular Pathways and Disease Severity

Severe COVID-19 disproportionately impacts patients with comorbidities such as type 1 diabetes (T1D), type 2 diabetes (T2D), obesity (OBCD), cardiovascular disease (CVD), hypertension (HTN), and cerebrovascular disease (CeVD), affecting 10–30% of cases. This study elucidates shared molecular mechani...

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Bibliographic Details
Main Authors: Suresh Kumar, Jia-Jin Wee, K. J. Senthil Kumar
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:COVID
Subjects:
COVID-19
comorbidities
bioinformatics
interactome analysis
hub genes
Online Access:https://www.mdpi.com/2673-8112/5/7/105
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Summary:Severe COVID-19 disproportionately impacts patients with comorbidities such as type 1 diabetes (T1D), type 2 diabetes (T2D), obesity (OBCD), cardiovascular disease (CVD), hypertension (HTN), and cerebrovascular disease (CeVD), affecting 10–30% of cases. This study elucidates shared molecular mechanisms by identifying common hub genes and genetic variants across these conditions using an integrative bioinformatics approach. We curated 5463 COVID-19-related genes from DisGeNET, GeneCards, T-HOD, and other databases, comparing them with gene sets for T1D (324 genes), T2D (497), OBCD (835), CVD (1756), HTN (837), and CeVD (1421). Functional similarity analysis via ToppGene, hub gene prediction with cytoHubba, and Cytoscape-based protein–protein interaction networks identified four hub genes—<i>CCL2</i>, <i>IL6</i>, <i>IL10</i>, and <i>TLR4</i>—consistently shared across all conditions (<i>p</i> < 1.0 × 10<sup>−5</sup>). Enrichr-based gene ontology and KEGG analyses revealed cytokine signaling and inflammation as key drivers of COVID-19 cytokine storms. Polymorphisms like <i>IL6</i> rs1800795 and <i>TLR4</i> rs4986790 contribute to immune dysregulation, consistent with previous genomic studies. These genes suggest therapeutic targets, such as tocilizumab for <i>IL6</i>-driven inflammation. While computational, requiring biochemical validation, this study illuminates shared pathways, advancing prospects for precision medicine and multi-omics research in high-risk COVID-19 populations.
ISSN:2673-8112

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