Candidate gene studies have identified several genes that affect cardiac depolarization and conduction measured by ECG traits. One set of candidates consists of genes that encode voltage gated potassium and sodium channels, which also play an important role in the pathophysiology of long QT syndrome (Lai et al. 1994; Splawski et al. 2002; Wang et al. 1996; Wang et al. 1995a; Wang et al. 1995b). These associations have been confirmed by molecular genetic studies, and, in the past five years, GWAS have also identified these associations with various ECG phenotypes in European and Asian-descent populations (Chambers et al. 2010; Newton-Cheh et al. 2009; Smith et al. 2009). These GWAS have not only implicated common variation in congenital long QT syndrome genes, but also have identified associations between genes not previously implicated in cardiac electrophysiology and ECG traits, such as NOS1AP with QT interval (Arking et al. 2006; Post et al. 2007). Genome-wide association studies for ECG traits have also revealed pleiotropy: for example, variants in the cardiac sodium channel gene SCN5A, has been associated with across multiple ECG traits (Holm
