Paloma Jordà, University of Montreal

The genetic basis and heritability of cardiovascular diseases (CVDs) are well demonstrated, with a genetic makeup ranging from common low-risk genetic variants (SNPs) to rare high-risk genetic variants that may cumulatively contribute to the phenotypical expression of a particular condition. Heritable cardiac disorders, specifically channelopathies and cardiomyopathies, leading known causes of sudden cardiac death among young individuals, have been classically considered to have a Mendelian inheritance. Recent data have demonstrated a significant contribution of common genetic variants also in the so-called Mendelian diseases. In this more comprehensive paradigm the presence of a “pathogenic variant” is not always necessary or sufficient for phenotypic manifestation, but the disease may manifest under near monogenic, oligogenic or polygenic models. Identification of the common genetic variation underlying the etiology of these diseases contributes to the understanding of their mechanisms and to the discovery of potential therapeutic targets. In addition, aggregation of multiple SNPs in so-called polygenic scores have demonstrated to be useful in predicting disease expression and prognosis of these diseases.