Article By: Wexner Medical Centre
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Researchers at The Ohio State University, led an international group of experts that worked together to classify 19 genes associated with dilated cardiomyopathy as having high impact on the heart muscle disease.
Researchers believe most of DCM has a genetic background, and at least 30 percent of people with DCM have a family member with the disease. First-degree family members (daughters, sons, brothers, sisters and parents) of a patient with DCM are encouraged to undergo genetic testing for the disease.
However, current genetic testing panels analyse dozens, sometimes hundreds of genes, and they often have limited scientific support, making genetic results clinically difficult to interpret.
“When we get results back for a patient with dilated cardiomyopathy, we often see multiple variants in multiple genes. For many genes, we don’t know how strongly they’re associated with the condition. By narrowing down the number of genes thought to be disease causing to 19, we can better use genetic information for a diagnosis and give the family a genetic marker to test family members not showing any signs of the disease. Ideally, we can then find who is at risk before they develop DCM,” said Elizabeth Jordan, a genetic counsellor in the Division of Human Genetics at the Ohio State Wexner Medical Centre, and lead author on the study published in the American Heart Association’s Circulation.
Dilated cardiomyopathy is a condition in which the heart muscle weakens and the left ventricle enlarges. It’s the most common cause for patients needing a heart transplant and is responsible for about half of heart failure cases.
For the yearlong study, Stephanie Schulte, head of research and education services at the Health Sciences Library at The Ohio State University, helped develop an initial list of 267 genes after examining various databases. Jordan, along with co-author Laiken Peterson, a genetic counsellor at The Ohio State University College of Medicine, and senior author, Dr. Ray Hershberger, division director of human genetics at the Ohio State Wexner Medical Centre and a researcher at the Dorothy M. Davis Heart and Lung Research Institute, narrowed the list down to 51, which was evaluated by an international panel of genetic counsellors, cardiologists and laboratory scientists.
They used a method developed by the National Institute of Health’s Clinical Genome Resource (ClinGen) to determine which genes were most strongly associated with DCM. The research was funded by the NIH’s National Human Genome Research Institute and the National Heart, Lung, and Blood Institute.
“The researchers evaluated clinical data in humans as well as experimental data in animal models to determine the likelihood that a gene had a role in the disease,” Jordan said. “Because we often see uncertain genetic results with dilated cardiomyopathy, our hope is that our findings will aid in the interpretation of results of large genetic testing panels, which should help genetic information be more useful in clinical care.”
The findings will be extended by research currently being done by the Dilated Cardiomyopathy Consortium, led by Hershberger. In 2015, the NIH awarded $12.4 million to the consortium to study the genetic basis of DCM and lay the foundation for precision medicine for patients.
“This was a great example of collaboration with genetic experts across the world. This research, along with additional work being done at The Ohio State University Wexner Medical Centre, will provide a better understanding of the role of genetics with DCM and how to treat and prevent it,” Hershberger said.