A new study using data from over 60,000 individuals has identified 67 genes that influence the heart’s ability to pump blood. The findings, published in the Journal of the American College of Cardiology, could help identify new therapeutic targets to prevent or manage a number of conditions affecting the heart.
“These results will kick-start numerous projects to determine the role of each gene in heart function,” said Rolf Bodmer, PhD, professor and director of the Development, Aging, and Regeneration Program, who contributed to the study. “We started that process in this paper by looking at how a few genes affect the heart in animal models, but there are many more to be explored.”
The new investigation involved the collective efforts of more than 100 scientists from 17 countries, led by Pim van der Harst, MD, of University Medical Center Groningen in the Netherlands. The team analyzed previously collected data including electrical tracings of heart activity—electrocardiograms or EKGs—and gene sequence variations across the entire genome in each individual. This identified 52 locations in the genome where a variation in the DNA was associated with changes in EKG recordings. Searching for nearby genes that are active in the heart then led to the 67 candidate genes that may be involved in establishing and maintaining normal heart function.
Many of these genes had not previously been known to affect how the heart works. To start figuring out what they do, researchers in the Bodmer lab used the genetic tools available in the fruit fly, Drosophila, to switch a handful of the top candidate genes off, one by one.
One of these, NACalpha, stood out because without it, the heart breaks down before the fly reaches adulthood. Because they lack a heart, these flies die shortly thereafter.
“We know what NACalpha and the products of related genes do in cells—they help proteins go to the right place as they’re being synthesized,” said Bodmer. “But we don’t know why NACalpha function is so critical specifically for the heart to form and work properly. We’re now trying to answer that question by looking at its interactions with other proteins, again using the fruit fly as a model system.”
“Because NACalpha affects heart development, we think that understanding its function could lead to better diagnostics and treatments for congenital and other heart diseases,” Bodmer added.
The list of candidate genes might soon benefit patients. “’Looking at patients’ specific gene variants is becoming common practice,” said van der Harst. “We will soon be able to link these genes to the risk of heart problems. That information could lead to tests that predict patients’ risk of heart failure, for example.”
This story is based in part on a press release from the University of Groningen.
The paper is available online here.