Skipping a beat, genes and heartbeat

Researchers have identified 22 regions of the human genome responsible for controlling the rhythm of heartbeats, according to an international study published in Nature Genetics. The findings may help explain the development of those with irregular heartbeat and who may have an increased risk of heart problems.

'By understanding more about the biological processes that control every heart beat, we can begin to have real insight into causes and potential treatments for people at increased risk of sudden death, heart failure and cardiac mortality', said Dr Caroline Hayward from the MRC Human Genetics Unit in Edinburgh, a scientist involved in the analysis.

The scientists conducted an electrocardiogram (ECG) on almost 50,000 people to measure their heart's electrical activity before analysing their genetic code. They were able to identify the genes associated with recorded variations in the electrical pulses that regulate the heartbeat.

Normally, signals start from specialised muscle cells, travel across the heart and cause rhythmical muscle contractions or heartbeats - a system called cardiac conduction. The signals register as the pulsating wave seen on heart monitors, such as the ECG. An irregular heartbeat can make people more susceptible to heart failure, sudden death, and death due to heart disease.

Some of the genetic variations were found in two sodium channel genes that sit side-by-side on the human genome. Sodium channels are molecular gated pores in living cells that control the flow of sodium ions - electrically charged particles - critical for a heartbeat.

The first gene, SCN5A, is well known to be involved in cardiac conduction. The second, SCN10A, has only recently been found in the heart. The researchers also found a number of other genes and genetic pathways involved in cardiac conduction, including calcium handling processes and transcription factors which influence heart development and formation. For example, dysfunctions in these processes before birth could lead to newborns with malformed hearts.

Dr Jim Wilson from Royal Society University Research Fellow at the University of Edinburgh, said: 'This study demonstrates the great potential of modern genetics to help us better understand how our heart's electrical system works at the molecular level. This is very important as heart conduction abnormalities increase the risk of heart failure and sudden death: this knowledge will be used in the hunt for new treatments'.

The data came from a consortium of 15 European and American studies. More than 100 scientists from the UK, Europe and the US contributed to the work. The project was funded by the National Institutes of Health (NIH), the Medical Research Council (MRC), the Chief Scientist Office, and the Royal Society. UK universities taking part in the research include the University of Edinburgh, the University of Leicester and the University of Glasgow.