Genome-wide analysis of left ventricular image-derived phenotypes

What is it about?

The size and function of the heart undergo changes due to lifestyle factors and cardiovascular diseases. Abnormal and extreme structural alterations of the heart can lead to heart failure, which is known to cause disabling symptoms and premature death. Previous research has shown that differences in the heart size and function in a general population are partly influenced by genes, but the extent of genetic influence is poorly understood. This study sought to quantify the amount genetic contributions (known as heritability) and identify the genes associated with variation in the size and function of left ventricle, the main pumping chamber of the heart. We used the measurement data from approximately 17,000 individuals in the UK Biobank medical research project, which provided the heart magnetic resonance images (MRI) and the genetic information. We applied an artificial intelligence (AI) tool to measure the volume and function of left ventricle in 17,000 healthy volunteers and investigated the genetic markers that are associated with variation in the morphology of left ventricle. We found that the size and function of left ventricle are highly heritable – approximately 22% to 39% of variation in the left ventricular structure and function is determined by the genetic differences between individuals. The degree of heritability is overall stronger than other comparable cardiovascular traits such as heart rate or blood pressure. We identified a total of fourteen regions in the human genome associated with the structure and function of left ventricle. These regions contain genes involved in the early development of heart chambers and regulations of the contractility of heart muscle. Several key genes identified in this study were implicated in the development of heart failure. Using the information obtained from our analysis models, we constructed the genetic risk scores which can identify individuals at a higher risk of heart failure.

Featured Image

Why is it important?

This study used the state-of-the-art AI technique to automatically measure the heart MRI images at scale. This approach enabled the completion of one of the largest genetic association studies of heart MRI measurements and provided a blueprint for future genetic studies utilising the heart MRI images. The results indicate that the human genetic variations play a significant role in determining the individual differences in heart morphology. Several genes known to be important in heart failure also appear to regulate the heart size and function even in the individuals free from major cardiac diseases.

Perspectives