Unraveling the genetics of feline hypertrophic cardiomyopathy: A multiomics study of 138 cats

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac
disease in cats, often leading to congestive heart failure, arterial
thromboembolism, and sudden cardiac death. The genetics of feline HCM are
poorly understood, and limited genetic discoveries remain breed or
family-specific. We aimed to identify novel causative or disease-modifying
variants in a large cohort of cats reflective of the general cat
population. In a second cohort, we sought to characterize transcriptomic
differences between HCM-affected cats and healthy controls. DNA was
isolated from 138 domestic cats (109 HCM and 29 controls). No single or
combination of variants of high, moderate, or modifying impact were
identified in genome-wide analysis to cause or modify the disease severity
of HCM. Several rare high and moderate-impact variants in genes associated
with human HCM were detected in diseased cats. In a second cohort, left
ventricular (LV), interventricular septal (IVS), and left atrial (LA)
tissues of 27 HCM-affected and 15 control cats were submitted for stranded
mature RNA-sequencing at 50 million reads/sample. A total of 74, 115, and
45 DEGs were upregulated and 8, 53, and 48 DEGs were downregulated in
LVPW, IVS, and LA tissue, respectively, in HCM-affected cats compared to
controls. Similar to humans, the genetic etiology of feline HCM remains
unknown in a high proportion of cases. Transcriptomics revealed molecular
signatures that may help identify novel HCM biomarkers or drug targets in
future investigations.