Genomic research is helping the medical profession identify and target the specific genetic variants and risk factors associated with life-threatening illnesses. It’s part of growing focus on “precision” medicine aimed at deterring or slowing the progression of these illnesses in young asymptomatic patients whose genetic makeup predisposes them to become disease victims with reduced chances of survival later in life. In fact, genome sequencing may reduce the risk of heart failure.
According to the CDC, some 6.2 million Americans suffer some form of heart failure, and about 300,000 die annually from sudden heart attacks. Once heart disease becomes advanced, especially in those over 50, the risk of early death, possibly by cardiac arrest, increases exponentially.
Genomic researchers at Northwestern University have taken a special interest in heart disease and its consequences. In a recent study funded by the National Institute of Health and several foundations, a team led by Megan Roy-Puckelwarz, PhD and Kathryn McNally, PhD examined the genomes and ancestries of more than 115,000 patients experiencing heart failure and were able to identify 47 risk loci in the human genome that seem to predict the likelihood of its occurrence.
The team also tested for 725 common proteins in the patient sample and identified nine proteins specifically associated with heart failure – a breakthrough finding with enormous implications for successful early medical intervention.
“This study opens up new ways to think about heart failure,” said Puckelwartz, an assistant professor of pharmacology at Northwestern who co-authored the study. “These loci now become a target for treatment and because we also show the strength of association between heart failure and these cardiometabolic imaging traits, we can use these as markers to determine someone’s risk of heart failure.”
Previously, only 11 common risk loci for heart failure had been identified using a method known as “genome-wide association,” which links genetic variants across the genome with a patient’s health condition. But Puckelwarz and McNally were able to compile an unusually robust sample of heart failure patients with diverse genetic profiles; they also tested for specific cardiometabolic traits, including atrial fibrillation, body mass index, coronary artery disease, blood pressure and cholesterol levels, that might be associated with heart failure. The scope and depth of their research was unprecedented.
“This study is important because of the size and scope of the heart failure populations that participated,” said McNally, the Elizabeth J. Ward Professor of Genetic Medicine at Northwestern and a trained physician. “By evaluating such a large number of heart failure patients, it was possible to find new genes and proteins implicated in heart failure.”
Ruckelwartz and McNally are hopeful that appropriate pharmaco-kinetic treatments might now be offered to genetically-profiled patients to reduce their risk of developing severe heart disease and eventually suffering heart failure.
But more genomic research is still needed. “We hope to build from these observations and to integrate rare gene changes with these types of ‘common’ gene variants so that we can better predict who is likely to progress to heart failure and who may be likely to develop arrhythmia complications,” McNally said.
The two researchers said they plan to solicit a follow-up grant from the NIH, the American Heart Association’s Strategically Funded Research Network on Arrhythmias and Sudden Cardiac Death, and the Leducq Foundation to support the additional research. For a review of their recent findings, see the November 2022 issue of Nature Communications.