video:
Built from MRI data this video shows how the heart muscle contracts (strain) which the researchers used to find genetic associations.
Credit: Professor Declan O’Regan, MRC Laboratory of Medical Sciences
A major cardiovascular risk factor is thickening of the heart walls (hypertrophy) which can results 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 certain genetic factors can influence how an individual’s heart will remodel affecting susceptibility to hypertrophic heart disease later in life. Understanding these genetic determinants could allow the earlier identification of people who may be at greater risk for unhealthy heart remodelling 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, reported today in Circulation: 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 of hypertrophy, 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 with genetic and data from over 40,000 people, they discovered 42 new genetic locations (loci) that influence remodelling and hypertrophy of the left ventricle of which 18 could not be identified using traditional GWAS techniques.
This research was funded by the British Heart Foundation, the Medical Research Council, the Engineering and Physical Sciences Research Council, the Sir Jules Thorn Charitable Trust, the NIHR Imperial College Biomedical Research Centre and the NIHR University College London Biomedical Research Centre.
Journal
Circulation Genomic and Precision Medicine
Method of Research
Computational simulation/modeling
Subject of Research
People
Article Title
New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping
Article Publication Date
7-Oct-2025
COI Statement
Dr O’Regan has consulted for Bayer AG and Bristol Myers Squibb. Dr Ware has consulted for MyoKardia, Inc, Pfizer, Foresite Labs, Health Lumen, and Tenaya Therapeutics, and received research support from Bristol Myers Squibb. Dr McGurk has consulted for Checkpoint Capital LP. Dr Zheng has consulted for Health Lumen. None of these activities is directly related to the work presented here. The other authors report no conflicts.
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