While scientists have known that genes play a role in the development of heart disease, new work has shown that the genetic contribution is larger than thought. An international team of researchers determined that genetic factors contribute around 30 percent or more of the risk of heart disease. The findings have been reported in the Journal of the American College of Cardiology and are outlined in the video.
When plaque builds up on the walls of arteries and blocks blood flow, it can lead to the most common kind of heart disease - coronary artery disease (CAD). Studies that look for small variations in the sequences of genes that are associated with some disease are called genome-wide association studies (GWAS), and they can help identify the causes of complex diseases that involve many genes, such as heart disease. GWAS studies of CAD had suggested that less than 25 percent of CAD cases were due to genetic influences. Researchers then decided to check variations in genes that control the expression of other genes to see if any variants in gene regulatory networks (GRNs) were involved in the development of CAD.
In this work, two sets of CAD patients were assessed to see how genetic variations in GRNs impacted their disease. The scientists found 28 separate GRNs that are related to CAD. Small changes in the sequences of genes in those networks accounted for another eleven percent of CAD risk. This work raises the heritability of CAD to around 32 percent. The disease appears to arise from a complex interplay between environmental factors like diet and exercise with variations in both protein-coding and regulatory genes.
“The results of this study demonstrate that the risk of heart disease is a concerted result of interactions between genetic variants and biological environments,” explained Johan LM Björkegren, a Professor of Medicine (Cardiology), and Genetics at the Icahn School of Medicine at Mount Sinai. “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.”
“A mystery of recent research was the fact that many genes contributing to the genetics of coronary artery disease affect mechanisms that were not expected in this context. The present study leads to a much better understanding of how these genes work together in precipitating or preventing the disease,” added researcher Heribert Schunkert, M.D., Professor of Cardiology at the German Heart Center in Munich.