Abstract
Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.
Highlights
Dilated cardiomyopathy (DCM) is the most common cause of cardiac death in Irish Wolfhounds (IWH) [1, 2]
There were 36 individual dogs diagnosed with DCM included in the current study and 29 (80.5%) DCM affected individuals had a diagnosis of atrial fibrillation (AF)
Of the 12 that had been diagnosed with AF prior to DCM, 11 (91.7%) had been diagnosed with AF within 2 years, and all had DCM diagnosed within 3 years of their first AF diagnosis
Summary
Dilated cardiomyopathy (DCM) is the most common cause of cardiac death in Irish Wolfhounds (IWH) [1, 2]. In human DCM there is often a heritable genetic basis of this disease [3, 4]. In several dog breeds, including IWH, canine DCM has been shown to have heritable component [5,6,7]. The heritability of canine DCM and its clinical resemblance to human DCM suggest that there is a genetic basis to canine DCM [8, 9]. IWHs are not long lived with a median age at death in the UK population reported to be 7.04 years and a maximum reported age of 11.83 years [11]. There were 71 breeds with a median age at death higher than the IWH maximum reported age at death [11]
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