Unraveling the Genetics of Feline Hypertrophic Cardiomyopathy: Insights from a Multiomics Study of 138 Cats
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease affecting domestic cats. Characterized by thickening of the heart muscle, HCM often leads to serious complications including congestive heart failure, arterial thromboembolism, and sudden cardiac death. Despite its impact, the genetic causes of feline HCM remain largely elusive and previous findings have often been limited to specific breeds or family lines.
The Study: A Comprehensive Multiomics Approach
A recent large-scale multiomics study aimed to deepen the understanding of the genetics behind feline HCM by analyzing a diverse cohort of 138 domestic cats, including 109 cats diagnosed with HCM and 29 healthy controls. The goal was to identify novel genetic variants that might cause or modify the severity of the disease across a broad population representative of general domestic cats.
Key Findings in Genomic Analysis
Whole genome sequencing was performed on all cats in the study. Surprisingly, researchers found no single or combined genetic variants—whether of high, moderate, or modifying impact—that could conclusively explain the cause or severity of HCM in the general feline population. However, several rare genetic variants known to be associated with human HCM were detected in affected cats, suggesting possible shared pathways between species.
Transcriptomics Reveal Molecular Signatures
To complement the genomic data, the study included transcriptomic profiling using RNA sequencing of heart tissue samples from a second cohort of 27 HCM-affected cats and 15 controls. Researchers examined three key heart regions: the left ventricular posterior wall (LVPW), the interventricular septum (IVS), and the left atrium (LA).
In the LVPW, 74 genes were upregulated and 8 downregulated.
In the IVS, 115 genes were upregulated and 53 downregulated.
In the LA, 45 genes were upregulated and 48 downregulated.
These differentially expressed genes (DEGs) highlight complex molecular changes in feline HCM that mirror patterns seen in human cases, offering new clues about disease mechanisms.
Implications and Future Directions
The study confirms that, as in humans, the genetic basis of feline HCM remains unknown in many cases, emphasizing the need for ongoing research. The molecular signatures identified through transcriptomics could pave the way for the development of novel biomarkers or therapeutic targets, potentially improving early diagnosis and treatment options for cats affected by this devastating disease.
Conclusion
This multiomics study marks a significant advance in feline cardiovascular research by providing a comprehensive genetic and transcriptomic landscape of hypertrophic cardiomyopathy in domestic cats. While definitive causative variants remain undiscovered, the insights gained lay important groundwork for precision medicine approaches in veterinary cardiology.
