Genetics of sudden cardiac death

Numerous cardiac diseases may cause sudden cardiac death (SCD), and a genetic basis for SCD has been established in the inherited cardiac conditions (ICCs). Previously, ICCs were thought to have a Mendelian inheritance pattern, wherein a rare pathogenic/likely pathogenic variant in a known diseasecausing gene conferred risk. This inheritance model, however, could not explain a large proportion of cases.Advancements in genomic technology have facilitated application of genome-wide association studies (GWAS), allowing appreciation of the full spectrum of genetic variation in large populations. It has become clear that common variants may contribute to disease phenotype in ICCs as well, albeit with a smaller effect size and the need for additional factors. This has caused a shift in the understanding of inheritance patterns in ICCs, now thought to have a more complex, polygenic nature.Implementing this knowledge into genetic testing of SCD decedents will improve its diagnostic yield by identifying a subset of patients who do not carry a variant in one of the acknowledged disease-causing genes. It will also assist our understanding of modification of phenotype and potentially outcomes.