Genetics in a heartbeat

A large international consortium of researchers has identified dozens of genetic variants associated with individual differences in the electrical rhythm of the heart¹. 

The findings, published in Nature Genetics, provide fresh insights into heart function and identify candidate genes involved in cardiac arrest and various other heart conditions. 

The heart’s electrical activity can be measured using electrocardiography (ECG). ECG traces consist of three waves, named P, QRS, and T, each corresponding to the electrical signal associated with a specific part of the heartbeat cycle. The interval between points Q and T represents the contraction and relaxation of muscle tissue in the lower chambers. It can be prolonged in various conditions, triggering dangerous heart rhythms. 

The new study was led by Dan Arking of Johns Hopkins University School of Medicine, and included researchers from the King Abdulaziz University and Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders in Jeddah. They analysed genomic, proteomic and transcriptome date from around 100,000 people, and identified 22 common single nucleotide polymorphisms (SNPs) which, together with 12 previously identified variants, account for 8–10% of the variation in QT interval.

Five of the variants are found within genes encoding some of the sodium and potassium channels that regulate the electrical activity of muscle cells. Mutations in each of these genes have previously been shown to cause Long QT Syndrome, an uncommon heart condition that can cause fainting and an abnormally fast heart rhythm.

Others are located within genes encoding proteins involved in regulating the concentration of calcium ions in heart muscle cells. The findings could help clinicians identify people at risk of heart conditions.  

The team will now try to identify the mechanisms by which each variant alters the electrical activity of heart muscle cells. 

“We will test how these variants influence risk of drug-induced arrhythmia in people who take any of 80 marketed drugs that prolong the QT interval, and test the common ones for their ability to identify Long QT Syndrome individuals who are at high risk for sudden death, and who may therefore benefit from implantation of a defibrillator,” says senior author Christopher Newton-Cheh of Harvard Medical School.”