Unraveling the Puzzle of the Role of Heritability in the Variability of the QT Interval Using Exome Array Analysis
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
See Article by Bihlmeyer et al
Since the discovery the intricate structure of DNA by Watson and Crick1 and the completion of sequencing of the entire human genome only a few decades later,2 genomic medicine has taken large strides in discovering novel disease-causing genes and modifiers in an effort to better diagnose, manage, and treat various diseases. The ultimate goal of all these studies is the one of personalized medicines catered to a person’s unique genomic fingerprint. Not only have the sequencing techniques become significantly cheaper—and even affordable to be used as mail-order kits—genome and exome data sets have become large enough to perform large consortium studies to find novel genes or loci associated with common traits, such as QT prolongation on the surface ECG.
QT prolongation is associated with a risk for significant ventricular arrhythmias, torsades de pointes, and sometimes ventricular fibrillation and sudden cardiac death. Not only is QT prolongation the pathognomonic feature of the rare, inherited condition known as congenital long-QT syndrome (LQTS; estimated prevalence 1 in 2000 individuals),3 it is often associated with far more common conditions, such as electrolyte imbalances (especially potassium and magnesium), certain comorbidities, or in combination with prescription medications known to effect the QT interval, such as ondansetron or amiodarone.4 In fact, attenuation of the QT interval is one of most common reasons of US Food and Drug Administration black box warnings or medications being halted in development because of the risk of sudden cardiac death.5 And although the genetic causes for approximately 80% of the predominantly autosomal dominantly inherited LQTS have been established, the genetic fingerprint of QT vulnerability for the general population, for example, that what …