byMRC Laboratory of Medical Sciences

Cardiac image analysis. Credit:Circulation: Genomic and Precision Medicine(2025). DOI: 10.1161/circgen.124.005116

A major cardiovascular risk factor is thickening of the heart walls (hypertrophy), which can result from high blood pressure—but is also linked to inherited diseases of the heart which can lead to sudden death.

The human heart comprises 4 chambers; two atria (on top) and two ventricles (at the bottom). The left ventricle is the main pumping chamber which needs to adapt to changing demands placed on the heart. Recent research has shown that certaingenetic factorscan influence how an individual's heart will remodel, affecting susceptibility to hypertrophic heart disease later in life.

Understanding thesegenetic determinantscould allow the earlier identification of people who may be at greater risk for unhealthy heart remodeling and inform early interventions to protect long-term cardiac health. This work has also highlighted genes that could potentially be linked to excessive thickening of the heart muscle that occurs in families—a disease called hypertrophic cardiomyopathy.

In a world first,reportedtoday inCirculation: Genomics and Precision Medicine, the computational cardiac imaging group team at the LMS, headed by Professor Declan O'Regan, conducted the first ever three-dimensional, genome wide analysis study (3D GWAS) of the heart.

"This work will help to identify potential new causes or modifiers ofhypertrophy, which we know is a key risk factor for poor health outcomes," said Declan.

Traditionally, GWAS studies looked for links between physical traits and genetic variations throughout the entire DNA sequence. In this study, the researchers used three-dimensional MRI images of the heart to see if variations in structure could be linked to variations in DNA. By integrating MRI-derived structural imaging data withgenetic datafrom over 40,000 people, they discovered 42 new genetic locations (loci) that influence remodeling and hypertrophy of theleft ventricle, of which 18 could not be identified using traditional GWAS techniques.

More information: Chang Lu et al, New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping, Circulation: Genomic and Precision Medicine (2025). DOI: 10.1161/circgen.124.005116

Provided by MRC Laboratory of Medical Sciences