Genetics of Sudden Cardiac Arrest: Overview of Genetic Risk Factors and Aetiologies

Sudden cardiac death (SCD) is one of the leading causes of death worldwide. Coronary artery disease (CAD) is the predominant cause of SCD in older individuals, while inherited cardiomyopathies and channelopathies are more common in younger individuals under the age of 35 years. Genetic disorders associated with SCD have traditionally been perceived as monogenic disorders. However, increasing evidence suggests that many of these disorders have complex genetic architecture with contributions from multiple genetic variants, known as polygenic inheritance, along with environmental factors. Improved understanding of genetic contributions and variants in SCD may help elucidate the cause of SCD, enable risk stratification, and identify novel disease mechanisms to guide preventative and therapeutic strategies in SCD. This review provides an overview of the genetic risk factors and clinical implications for the most common cardiac disorders related to SCD in both old and young individuals: specifically CAD, as well as the inherited cardiomyopathies and channelopathies, respectively.