One in 100 people have genetic variations that can cause potentially life-threatening heart conditions, including high cholesterol (lipid disorders), heart muscle disease (cardiomyopathies), and abnormal heart rhythms (arrhythmias).
Yet the functional impact of most of these cardiovascular genetic variants — whether they disrupt normal function or are harmless — is unknown. That is about to change.
Researchers from Vanderbilt University Medical Center, Stanford Medicine, the University of Toronto and Brigham and Women’s Hospital in Boston have joined forces to “map” the specific variations in more than 25 key cardiac disease genes that negatively affect heart function.
Funded by a four-year, $8.2-million grant from the National Health Lung and Blood Institute of the National Institutes of Health (NIH), their newly formed CardioVar Consortium will generate a comprehensive atlas of “variant effect maps” to distinguish disease-causing variants from those that are harmless.
The goal is to illuminate the molecular mechanisms of cardiovascular diseases, the leading causes of death and disability worldwide, and 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, who holds the Sam L. Clark, MD, PhD, Endowed Chair in the Vanderbilt University School of Medicine, is known internationally for his studies of arrhythmias and of the role that genetic variations can play in adverse drug reactions.