Sarah Abramowitz, BA, a medical student at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and a Sarnoff Cardiovascular Research Fellow, published her research highlighting the inconsistencies of polygenic risk scores (PRSs) in the Journal of the American Medical Association (JAMA) on November 16, 2024. On the same day, she presented her findings at the American Heart Association’s Scientific Sessions in Chicago, where she was the only student finalist in the Genomic and Precision Medicine Early Career Investigator Competition. The study, conducted during Abramowitz’s Sarnoff Fellowship at the University of Pennsylvania’s Perelman School of Medicine, examines the variability of PRSs in predicting coronary artery disease (CAD) risk. The research was supported by the National Institutes of Health, the Sarnoff Cardiovascular Research Foundation, and the US Department of Veterans Affairs.
“We are proud of Sarah’s outstanding achievement of having her research published in JAMA and presented at the AHA Scientific Sessions,” stated Joel N.H. Stern, PhD, SFACAAI, director of the Office of Medical Student Research and professor of neurology, molecular medicine, urology, and science education. “This milestone demonstrates her dedication and hard work as a researcher and underscores her exemplary leadership qualities and promising future as both a physician and scientist.”
PRSs are a cutting-edge tool in genetics that combine information from genetic markers across the genome to estimate an individual’s risk of developing certain diseases. However, Abramowitz and her research team found significant individual-level variability across currently available PRS scores. “Our research underscores a critical gap in our understanding of PRSs, which has implications for their use in personalized medicine,” said Abramowitz, the study’s lead author. “While these scores show promise for population-level CAD risk assessment, we need more robust methods to quantify and communicate the uncertainty of individual-level predictions.”
The researchers analyzed data from over 260,000 diverse participants and found that while most PRSs performed similarly in predicting CAD risk at the population level, individual-level predictions varied widely. Many participants were categorized as both high and low risk by different PRSs, raising concerns about the potential for conflicting medical advice based on the score used.
“Polygenic risk scores represent an exciting frontier in personalized medicine and are gaining traction in clinics and as commercial health tests, but our findings suggest they need to be used carefully,” said Michael G. Levin, MD, assistant professor of Cardiovascular Medicine and cardiologist at Penn and the Corporal Michael Crescenz VA Medical Center (CMCVAMC), and a co-author of the study. “At the individual level, these scores can vary quite a bit, meaning the same patient could receive dramatically different risk assessments that impact how doctors make decisions about prevention and treatment.”
The research, which used data from the All of Us Research Program, Penn Medicine Biobank, and UCLA ATLAS Precision Health Biobank, compared 48 different CAD PRSs. While 46 scores provided similar population-level predictions, 20% of participants had at least one score placing them in both the highest and lowest 5% of risk.
“The goal of PRSs is to help identify people at higher genetic risk for diseases like heart disease,” explained Scott M. Damrauer, MD, vice chair for Clinical Research in Penn’s Department of Surgery and a vascular surgeon at Penn and the CMCVAMC. “But for clinical use, it’s crucial that the results are consistent and reliable, especially when decisions about someone’s health are at stake.”
The study’s findings highlight the need for further refinement before PRSs can be widely adopted in healthcare to guide individual CAD risk assessment. Researchers recommend that clinicians consider potential inconsistencies and use these scores as part of a broader risk assessment strategy that includes clinical and lifestyle factors.
Abramowitz, who hails from Menlo Park, California, is the first student from the Zucker School of Medicine to be named a Sarnoff Cardiovascular Research Fellow. This summer, she began her second year in this prestigious program, which supports students from accredited U.S. medical schools in pursuing cardiovascular disease research. Abramowitz was also one of five finalists in the AHA’s Early Career Competition, presenting her research at the 2024 AHA Scientific Sessions, held November 16–18 at the McCormick Place Convention Center in Chicago.
The Zucker School of Medicine has consistently been recognized as a best medical school for research by U.S. News & World Report. The institution was one of 16 that ranked in the top tier for research according to U.S. News 2024 Best Medical Schools for Research. To learn more about the Zucker School of Medicine’s research opportunities, click here.
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About the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Established in 2008, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell was founded by two equal partners: Hofstra University and Northwell Health. The School of Medicine is built upon the strong clinical and graduate medical education programs of Northwell, as well as the robust research and academic programs of both Hofstra and Northwell’s Feinstein Institutes for Medical Research. For nine years in a row, the Zucker School of Medicine has been recognized among the top medical schools nationwide for medical research (2016-2024, U.S. News & World Report’s Best Graduate Schools), and for the fourth year as one of the most diverse medical schools in the country (2021-2024, U.S. News & World Report’s Best Graduate Schools). The institution comprises more than 4,000 faculty members across 25 academic departments and enrolls a diverse community of over 400 students. For more information, visit medicine.hofstra.edu.
About Penn Medicine
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.
