Research opens the door to more accurate genetic testing for inherited diseases


Genetic testing colourful

New research allows scientists to better determine which gene mutations are responsible for inherited heart disease.

Despite technical advances allowing scientists to sequence DNA and gather genetic information about people, our ability to interpret that data has lagged behind.  This new study conducted by Professor Stuart Cook of the National Heart & Lung Institute (NHLI), in collaboration with Professor Hugh Watkins from University of Oxford, focused on understanding which genetic components are involved in inherited heart conditions, or cardiomyopathies. Cardiomyopathies are the most common cause of sudden death in otherwise healthy young people. These diseases of the heart muscle cause the heart to stop pumping blood as efficiently as it should, which can lead to heart failure or an irregular heartbeat.

This study has major implications for other diseases with strong genetic components as researchers can apply the same techniques to other studies using the ExAC database.

– Roddy Walsh


The study published in the journal Genetics in Medicine looked at the role of genes in inherited heart disease, by focusing on genes previously implicated as problem genes, responsible for inherited cardiomyopathies. Two genetic data sets were compared in the study, one of nearly 8,000 taken from patients with genetic cardiomyopathy, and one of more than 60,000 from the general population provided by the new ExAC database. The cardiomyopathy data set, from the Oxford Molecular Genetics Laboratory and the Laboratory of Molecular Medicine, Partners HealthCare in Boston, USA, is the biggest ever analysed. 

This research is concerned with rare genetic variants, or anomalies in a person’s genetic code, explained Dr James Ware a co-author on the paper. Until a few years ago people thought that if a variant was rare it must be problematic, but now researchers have realized that variants that are individually rare are collectively common, in fact we all have hundreds of such variants.  This includes variants that disrupt genes known to be linked disease, such as cardiomyopathy.  The majority of these people are healthy, and the variants have no ill effects.  Therefore, when we find a genetic abnormality in a patient with a genetic condition, we need to be really sure that it is responsible for their disease, and not just an innocent bystander.

This new research found that many of these ‘problem’ genes, that are often used in clinical genetic testing as indicators of heart disease, in fact show up no more often in heart patients than compared to the general population. This shows many genes previously claimed to cause cardiomyopathy are probably not linked at all - healthy people are just as likely to have variants in those genes as people with disease.

In addition, the research found that by looking at genes that really are linked to cardiomyopathy, variant interpretation could be markedly improved by focusing on variants that are ultra-rare, and looking for variants clustering in specific regions of genes that never vary in healthy people.  Using these new finding scientists can better distinguish between the important disease-causing variants and the innocent bystanders.  This will improve genetic testing results, and allow more patients to benefit from a robust genetic test.

Relatives of cardiomyopathy patients often undergo heart tests because the condition can be inherited. Those found to have no symptoms may have a genetic test to confirm they have the same gene variant as their family member, meaning they can be monitored and treated, often before the condition can be detected on conventional tests. Those who do not have the faulty gene can be reassured and avoid long-term follow-up, saving the NHS money. Currently, if genetic testing is inconclusive, relatives usually receive life-long care in case they later develop the condition. It is hoped the new research findings will lead to an increase in the number of conclusive diagnoses. 


Ms Helen Johnson

Ms Helen Johnson
National Heart & Lung Institute

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Cardiovascular, Genomics, Public-health
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