Genetic Variation and the Electrocardiograph
From Genome-Wide Association Studies to the Patient
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See Article by Lin et al
Genome-wide association studies (GWAS) have revolutionized the study of disease biology, the genetics of common complex diseases, and have greatly improved our understanding of the myriads of pathways amenable to pharmacological intervention. Gradually, we are witnessing the translation of GWAS findings into patient care through the definition of risk profiles and identification of biomarkers.1
The heritability of cardiovascular traits, such as electrocardiograph (ECG) parameters, is of particular interest in cardiology. ECG is a valuable tool in determining the presence of many cardiovascular conditions, including structural derangements, arrhythmias, infarctions, and conduction disturbances. Better understanding of the genetics behind cardiovascular conditions will enhance the understanding of the pathophysiological basis of these diseases, help identify novel pharmacological targets, as well as contribute to risk assessment and clinical management of patients. Since Arking et al2 identified a common NOS1AP variant, which modulates cardiac repolarization, over a decade ago, GWAS has been applied to several ECG parameters. However, an examination of heritability of ECG traits determined that although 35% to 55% of the variance, seen in twin and family studies, can be explained by genetics, only 10% of the total trait variability have been identified using GWAS.3 This is despite increasing sample sizes and the concomitant increase in discoveries of common variants scattered throughout the genome.4 Furthermore, GWAS data are largely generated in populations of European ancestry. It is important to expand our knowledge of genetic variation and disease association in multiple populations along with examining rare variants, both in a bid to combat the phenomenon of missing heterozygosity, which plagues GWAS, but also to target genes and genetic …