Integrated Analysis to Identify the Roles of NAV2 in Liver Fibrosis and Atrial Fibrillation

Although there is substantial clinical comorbidity between atrial fibrillation and liver fibrosis, it is still unknown what molecular processes these conditions share.

This study aims to identify key co-disease genes for liver fibrosis and atrial fibrillation.

This study systematically identified and validated the pivotal role of NAV2 in both liver fibrosis and atrial fibrillation by integrating multiple transcriptomic datasets from the GEO database, employing a comprehensive analytical framework including differential expression analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction networks, multi-algorithm machine learning, SHapley Additive exPlanations (SHAP), Mendelian randomization, immune infiltration profiling, single-cell sequencing, and gene set enrichment analysis Results: A total of 147 comorbid genes were identified, with machine learning pinpointing 21 core genes. Among these, NAV2 was confirmed as the sole key gene via Mendelian randomisation, partially mediating the causal effect of liver fibrosis on atrial fibrillation (mediation proportion: 24.80%). Single-cell analysis revealed that NAV2 was highly expressed in atrial fibroblasts and hepatic epithelial cells. Gene Set Enrichment Analysis (GSEA) indicated NAV2 participation in metabolic, immune, and fibrosis-related pathways.

Epidemiological studies have long demonstrated the clinical comorbidity between liver fibrosis and atrial fibrillation, yet the molecular-level 'common drivers' remain unidentified. This study identifies key comorbid genes for liver fibrosis and atrial fibrillation.

NAV2 is a key mediating gene in the co-morbid mechanism of liver fibrosis and atrial fibrillation, demonstrating potential as both a biomarker and therapeutic target.