Heart disease is one of the leading causes of death globally. Two of the most common forms of heart disease include heart failure, where the organ becomes too weak to pump enough blood around the body, and arrythmia, where the heart beats abnormally.
Two large studies have taken a new approach to understanding the genetic factors behind these disorders and found hundreds of regions in the genome that contribute to the diseases, many of which have never been previously associated with heart disease.
The two teams of researchers, from Broad Institute of MIT and Harvard Massachusetts General Hospital studied data from thousands of patients to look for links between genetic variants, measurements of heart function and electrical activity and cardiac disease, and each identified a set of genetic factors.
The studies suggest new relationships between the genome and heart function and disease, which could provide clues about improving the way we identify and treat patients who are at high risk of developing heart disease.
The new approach to study cardiovascular genetics using measurements of cardiac mechanics and electrical conduction allows for the discovery of genetic regions contributing to cardiac disease susceptibility that was not previously possible.
Genetic influences on cardiac diseases have been studied extensively during the last ten years, but has been difficult to find common variants associated with heart failure or arrythmia because the these conditions are also associated with many subsets of disease, and the genetic analysis requires studying data from large groups of patients. The teams chose to examine data and cardiac measurements already available through various biobanks, which allowed them to focus on specific disease pathways and disentangle them from the broader syndromes of heart failure and arrythmia. They also chose to include data from people without disease which resulted in a larger study of sample sizes.
In the heart failure study, the team used cardiac magnetic resonance imaging (MRI) data from 36,041 patients of the UK biobank to quantify the mechanics of the left ventricle, and conducted a genome wide association study (GWAS) to search for common genetic variants associated with the structure and function of the ventricle. They found 45 novel genetic regions which appear to influence risk for various types of cardiomyopathy. The results showed that having a high burden of these variants can predispose people to dilated cardiomyopathy, which damages the organ and its ability to pump blood. Conversely, it showed that a very low burden of these variants was at increased risk of thickening of the muscle, which is a common cause of sudden death in athletes.
In the arrhythmia study, scientists from more than 140 institutions used the same approach to perform a GWAS study in search for abnormalities in the electrocardiogram (ECG). The ECG is widely used as a cardiac diagnostic test, and the investigators specifically studied the PR interval which reflects atrioventricular conduction associated with several common electrical disorders such as atrial fibrillation and bradarrythmias.
The study used a cohort of 293,051 people of European, African, Hispanic and Brazilian ancestry and they found 202 regions in the genome underlying cardiac conduction, 141 of which had not been previously identified. This is the largest genetic analysis of ECG trait to date, and more than tripled the known loci associated with atrioventricular conduction.
