Effort to map heart disease-causing genetic variations

Researchers from several leading organisations have joined forces to map the specific variations in more than 25 key cardiac disease genes which have a negative impact on heart function.

The newly formed CardioVar Consortium has been created by researchers from Vanderbilt University Medical Center, Stanford Medicine, the University of Toronto and Brigham and Women’s Hospital in Boston.

Together they want to create maps which distinguish disease-causing variants from those that are harmless to improve real-time diagnosis and early treatment.

“As genetic testing in patients with heart disease becomes increasingly adopted, a common result is a ‘variant of uncertain significance’,” said the grant’s principal investigator, Dan Roden, MD, Senior Vice President for Personalized Medicine at VUMC.

“Our high-throughput studies will provide data on function for thousands of variants – that will both help guide treatment for individual patients and provide insights into underlying biology.”

Roden’s co-principal investigators are Euan Ashley, MBChB, DPhil, professor of Medicine, Genetics and Biomedical Data Science at the Stanford School of Medicine and founding director of the Stanford Center for Inherited Cardiovascular Disease, and Frederick Roth, PhD, professor of Molecular Genetics and Computer Science at the University of Toronto’s Donnelly Centre and Departments of Molecular Genetics and Computer Science.

“At the current rate of clinical sequencing, it would take over 100 years to find most genetic variants relevant for heart disease even once in the population,” said Ashley, Associate Dean and Roger and Joelle Burnell Professor of Genomics and Precision Health at the Stanford School of Medicine.

“The variant maps we are building will allow us to dramatically accelerate that timeline, providing vital information for families we are seeing in clinic today.”

Roth, who is a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, and co-founder of the Atlas of Variant Effects Alliance, added: “Nearly every single DNA change that can occur already exists today in the human population.

“So why keep testing one variant at a time? We are grateful that the NIH is supporting our effort to get organized and start systematically testing all the variants.”

Another key co-investigator is Calum MacRae, MD, PhD, Vice Chair for Scientific Innovation at the Department of Medicine at Brigham and Women’s Hospital, Co-Director of the Genomic Medicine Clinic and Professor of Medicine at Harvard Medical School.

“Understanding the functional consequences of individual variants is the central requirement for interpreting genetic test results,” MacRae said.

“This project will transform clinicians’ ability to diagnose and manage every patient with inherited heart diseases.”