NEW YORK—A collaboration involving the Icahn School of Medicine at Mount Sinai, the German Heart Centre Munich, AstraZeneca and Karolinska Institutet in Sweden has demonstrated that more than 30 percent of heart disease risk stems from genetic factors, much more than was previously understood. The study findings, published in the Journal of the American College of Cardiology, introduce the biology of gene networks as a means to better understand the heritability and genetic underpinnings of heart disease.
Coronary artery disease (CAD), the most common type of heart disease and one of the leading causes of death worldwide, forms plaque in the walls of the arteries that supply blood to the heart. A complete blockage of these arteries can lead to a heart attack or stroke.
Before this study, more than a decade of genome-wide association studies had indicated that less than a quarter of CAD was considered inheritable. Meanwhile, the heritability contribution (if any) of genetic variants in gene regulatory networks (GRNs)—a set of genes that interact with each other to control a particular cell function—was unknown. In light of this, researchers used tissue data from two separate studies of individuals with CAD to determine whether genetic variants that regulate GRNs make independent contributions to the risk of heart disease.
They found that the genetic variation in these networks contributed to the inherited risk of the heart disease by an additional 11 percent—adding to the 22 percent attributable risk previously identified in genetic studies. This newfound contribution boosts the heritability of CAD to approximately 32 percent, spotlighting the important role played by interactions between internal environments and genetic variants—mediated by regulatory networks—in the development of heart disease.
“The results of this study demonstrate that the risk of heart disease is a concerted result of interactions between genetic variants and biological environments,” said Dr. Johan LM Björkegran, a professor of medicine (cardiology) and genetics at the Icahn School of Medicine. “By understanding the complex relationship between the two, we’ve created a framework for identifying new risk genes in disease-relevant tissues leading to heart disease, which in turn will allow for more effective risk prediction, clinical intervention and eventually, opportunities for novel and more effective therapies.”