In a study, published today in the journal Nature Genetics and part funded by the Medical Research Council and the British Heart Foundation, researchers showed that a risk score based on an individual’s genetic profile could help predict the likelihood of them developing hypertrophic cardiomyopathy (HCM), and also predict important disease complications. 

The researchers say that the insights the risk scores provide will help to inform monitoring and treatment for patients and their families. Those found to be at higher risk could be monitored more closely and offered treatments to reduce their risk of developing heart failure, abnormal heart rhythms, or cardiac arrest.  

Professor James Ware, Group Leader at the MRC Laboratory of Medical Sciences, and co-lead of the study, said: “Our patients and their families want to know what the future holds after a diagnosis of HCM, but it is extremely difficult to advise because it is such a variable condition. The same genetic change can lead to a fatal heart rhythm problem or a need for heart transplantation in some people, while others don’t manifest any problems at all. Thanks to this research, we’re an important step closer to being able to provide much needed clarity and reassurance. 

“We’ll need to replicate what we have found here in further studies, and developments will also be needed in NHS genetic testing services and data collection before this approach can be rolled out widely, but this is an important step in the right direction.” 

Around a third of cases are due to rare genetic faults in a single gene, usually inherited through families. More recently, this team of scientists discovered that so-called ‘common genetic variants’ can also cause HCM.  

A single common variant will have little impact on an individual’s risk of developing HCM, but the combined impact of many can significantly increase the chances. In those with a single rare genetic fault, the presence of common variants can also add to their already increased risk of developing HCM. 

An international team, led by researchers from the MRC Laboratory of Medical Sciences, Imperial College London, the University of Oxford, and Amsterdam University Medical Centre, generated a genomic risk score using genetic data from nearly 6,000 people with HCM and almost 70,000 people without the condition. The score estimates a person’s risk of developing HCM, or experiencing a complication, based on their DNA. 

The team tested their score using data from 640 people in the UK Biobank study who carry a rare genetic fault that can cause HCM. This showed that those with high risk scores (in the top 20 per cent) were nearly 10 times more likely to be diagnosed with HCM during their lifetime than those with scores in the lowest 20 per cent. 

Further testing in more than 1000 people who had already developed HCM showed that, compared to those with risk scores in the lowest 20 per cent, people with a risk score in the top 20 per cent were four to six times more likely to die in the years following their HCM diagnosis. They were also 3.5 times more likely to have had a serious adverse outcome including cardiac arrest, implantable cardioverter-defibrillator (ICD) implantation or heart transplant. 

The current risk score was developed and tested using data from a group of largely White European individuals. When tested, the researchers found that it initially performed much more poorly for individuals of South Asian, African and Chinese ancestry. But they found that adding data from fewer than 200 individuals with HCM from another ancestry was enough to significantly improve the score in that group.  

The team is partnering with patients and researchers from around the world to gather data representing a much wider range of ethnicities to develop and improve their score, and ensure it is effective for as many people as possible. 

Professor Metin Avkiran, Director of International Partnerships and Special Programmes at the British Heart Foundation, said: “In HCM, an enhanced ability to predict which patients are likely to develop the disease and its complications, which can be life-threatening, would allow doctors to direct care accordingly. This study is an important step in that direction.  

“Such an ability could also support effective application of future genetic treatments targeting the primary causal gene in patients where this is identified.” 

Publication: Zheng, S.L., Jurgens, S.J., McGurk, K.A. et al. Evaluation of polygenic scores for hypertrophic cardiomyopathy in the general population and across clinical settings. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02094-5