Traditionally, inherited cardiac diseases such as hypertrophic and dilated cardiomyopathies (HCM and DCM) have been considered to be monogenic diseases, caused by a single large-effect variant. But there is now mounting evidence of a polygenic contribution to these diseases. Whether an individual’s disease has a monogenic or polygenic cause may have implications around how they and their family members are managed. However, currently only monogenic variants are tested in the clinic. In Australia, a causal monogenic variant is only identified in around 30% of patients with an inherited cardiac disease. We hypothesise that testing for polygenic risk scores may help explain the cause of disease in a proportion of these patients which could inform the disease management strategy.
Using whole-genome sequence data in 433 individuals (216 female and 257 male) with a diagnosis of 4 different inherited cardiac diseases that are commonly seen in clinical practice, namely Atrial Fibrillation (AF), Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), and Long-QT Syndrome (LQTS) from the Australian Genomics Health Alliance cohort, we determine what proportion of individuals have a relevant PRS that is within the top 5th percentile of the population distribution, and may therefore imply a high polygenic burden as the cause for disease. Our findings will enhance our understanding of the clinical utility of PRS for supporting the diagnosis of inherited cardiac diseases.