Research suggests heart condition impacted by many rather than one single gene

Dilated cardiomyopathy (DCM) affects the heart’s ability to efficiently pump blood, as the organ grows larger but weaker.

It had been thought that the cause was faulty copies of one single gene inherited down family lines. However, in more cases than not, no specific gene can be identified as faulty.

Now a new study in Nature Genetics journal suggests that as much as one third of the risk is attributable to the cumulative but individually small effects of many thousands of genetic differences.

Co-senior author Dr Tom Lumbers, UCL Institute of Health Informatics and honorary consultant cardiologist at UCLH and Barts Health NHS Trusts, said:

“Our study also heralds a new way of thinking about the genetics of this heart disease. Instead of being caused by a single genetic spelling mistake, in some patients the condition is more like common diseases such as coronary artery disease, where many genetic differences collectively contribute to risk.

“Understanding the small effects of many genes across the genome also helps us to identify those patients carrying a faulty gene copy at highest risk of developing the disease.”

Analysing the results for 16 previous studies together with new data, the teams involved examined more than 14,000 DCM sufferers’ genomes and more than 1 million of individuals who did not have the disease.

They identified 80 areas of the genome with plausible links to the disease and within them, 62 specific genes likely to be linked to DCM. Most of the identified genome areas had not been linked previously.

After building a polygenic risk score, the researchers applied this to a new dataset: nearly 350,000 individual records stored in UK Biobank, which confirmed the effect of high polygenic risk scores.

Professor James Ware of Imperial College London & MRC Laboratory of Medical Sciences said: “We still have a lot of work to do to understand how these specific newly identified genes influence the risk of developing cardiomyopathy, but they are already shedding light on biological processes underlying the condition, and we hope that some will give new leads on possible treatments.

“One of our next steps is to explore integrating polygenic risk scores into genetic testing, to provide more people with a genetic explanation for their disease and a more precise assessment of disease risk.”

Pic: Robina Weermeijer