In a recent study from Northwestern Medicine, researchers have developed a new genetic risk score that more accurately predicts the likelihood of developing arrhythmia, an irregular heartbeat associated with conditions such as atrial fibrillation and sudden cardiac death.
The study, set to be published in Cell Reports Medicine on November 11, involved 1,119 participants. Scientists used whole genome sequencing to combine three genetic testing approaches: monogenic testing (which detects rare mutations in single genes), polygenic testing (which assesses multiple common gene variants), and full genome sequencing. This integrated method aims to provide a comprehensive assessment of disease risk.
Dr. Elizabeth McNally, co-corresponding author and director of the Center for Genetic Testing at Northwestern University Feinberg School of Medicine, explained the significance of the approach: “It’s a very cool approach in which we are combining rare gene variants with common gene variants and then adding in non-coding genome information. To our knowledge, no one has used this comprehensive approach before, so it’s really a roadmap of how to do that.”
McNally added that the findings could help develop therapies tailored to individual genetic profiles and allow physicians to identify risk before symptoms arise. “When you sequence the whole genome, you can say, ‘Let me look at this cardiomyopathy gene component, the gene panel and the polygenic component.’ By combining the data together, you get a very high odds ratio of identifying who is at highest risk, and that’s where we think this approach can really improve upon what is currently used,” she said.
Despite advances in genetic testing technology, McNally noted its use remains limited among physicians. She estimates that only 1% to 5% of people who should receive genetic testing actually do so; even in cancer care—where genetic links are well known—only 10% to 20% undergo such tests. “We need to improve uptake,” McNally said. “The biggest challenge is a workforce that isn’t trained in how to use genetic testing. As polygenic risk scores become more common, our approach will become even more valuable.”
The research team recruited 523 participants with arrhythmias (some also had heart failure) and reviewed their medical records thoroughly before sequencing their genomes. These results were compared against genomes from 596 control participants aged 40 or older without known cardiac disease history from the NUgene biobank.
“It was painstaking going through 500-plus records and making sure that the people in the study really belonged in the study,” McNally said.
Other Northwestern authors include Tanner Monroe, Megan Puckelwartz, Lorenzo Pesce, Dr. Alfred George and Dr. Gregory Webster. The project received funding from an American Heart Association Strategically Funded Research Network on Arrhythmias and Sudden Cardiac Death as well as support from the National Institutes of Health.