Background: Patients with rheumatoid arthritis (RA) have an increased risk of developing cardiovascular disease (CVD). However, the mechanisms underlying the comorbidity between RA and CVD remain poorly understood. This study aimed to identify the shared genes between RA and CVD and to explore their functional relationships.

Methods: Rheumatoid arthritis– and CVD-associated genes were obtained from the DisGeNET and Malacards databases, respectively. Shared genes between the 2 diseases were identified, and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using WebGestalt and Cytoscape (v3.9.0). To further investigate potential molecular interactions, protein–protein interaction networks were constructed based on data from the STRING database. Finally, the in silico Tabula Muris single-cell transcriptomic dataset was used to assess the tissue-specific expression of candidate genes and evaluate their potential roles in specific tissues and cell types.

Results: A total of 108 genes were shared between RA and CVD, out of the 898 and 552 genes identified for each condition. Functional enrichment analysis showed that these shared genes were predominantly associated with inflammation and immune response–related pathways. Among them, 42 candidate genes were identified, of which 7 (i.e., IFNG, CCL5, CXCL10, FN1, EGFR, CXCL1, and CD44) were highlighted based on their strong connectivity and biological relevance. For validation, the validation, Tabula Muris single-cell transcriptomic dataset revealed that these genes were highly expressed in mouse cardiac tissues.

Conclusion: Seven shared genes associated with both RA and CVD were identified, which may contribute to the comorbidity between the 2 diseases.