Nita Limdi, Ph.D., professor in the UAB Department of Neurology, is leading one of the largest real-world evaluations of genome-informed risk assessment in clinical care.Researchers at the University of Alabama at Birmingham are leading a large national effort to determine whether delivering personalized genetic risk information to patients and their doctors can meaningfully improve preventive health care for common chronic diseases.
Chronic diseases, including heart disease, diabetes, kidney disease and cancer, affect most Americans and account for more than 90 percent of United States health care spending. Historically, health care has focused on treating disease after it develops, rather than identifying people at high risk early enough to prevent illness or delay its onset.
A recent study published in the American Journal of Human Genetics outlines the design and analysis framework of one of the largest real-world evaluations to date of genome-informed risk assessment in clinical care. The research is led by Nita Limdi, Pharm.D., Ph.D., Ray L. Watts, M.D., - Heersink Endowed Chair in Neurology, professor and associate dean in the UAB Department of Neurology. It brings together investigators from the Electronic Medical Records and Genomics (eMERGE) Network, a National Institutes of Health-funded consortium of 10 major United States health systems including UAB, Vanderbilt University Medical Center, the University of Washington, Harvard Medical School/Mass General Brigham, Northwestern University, Mount Sinai Hospital, Mayo Clinic, Columbia University, Cincinnati Children’s Hospital Medical Center and Children’s Hospital of Philadelphia.
Advances in genomics have made it possible to estimate an individual’s inherited risk for certain conditions by analyzing many small genetic differences across the genome, commonly referred to as polygenic risk scores, or PRS, as well as rarer genetic variants with stronger effects. While these tools are increasingly available, there has historically been limited evidence showing whether providing this information improves real-world medical decision-making and clinical outcomes.
To address this gap, the eMERGE study has delivered genome-informed risk assessment reports to 23,840 adults and children, along with their health care providers, across participating sites nationwide. Each report combined genetic data with clinical factors and family health history to estimate risks for 11 common chronic conditions: asthma, atrial fibrillation, breast cancer, chronic kidney disease, coronary heart disease, colorectal cancer, hypercholesterolemia, obesity, prostate cancer, Type 1 diabetes and Type 2 diabetes. The reports included evidence-based recommendations for follow-up care, such as earlier screening, lifestyle changes, or additional clinical evaluation and treatment.
“The eMERGE study’s overarching goal is to determine whether PRS can be evaluated and applied to stratify individuals’ risk for multiple chronic conditions,” Limdi said. “Can PRS data, combined with other risk factors, be effectively incorporated into clinical workflows alongside recommended health care interventions? Will both providers and patients adopt these recommendations, and will such adoption improve clinical outcomes across a range of chronic diseases?”
The study is designed to track measurable outcomes within health care systems, including whether patients and providers follow recommended preventive actions, whether conditions are diagnosed earlier, and whether treatments are started or adjusted based on risk information.
To rigorously evaluate these outcomes, Limdi and the research team will use innovative quasi-experimental methods, including regression discontinuity, to help determine the impact of genetic information itself outside of a randomized clinical trial setting.
As genetic testing becomes more common, health care systems will need to integrate and facilitate the use of genomic risk information to guide care. Findings from this study will help inform future clinical guidelines, health system policies and research on the role of genomics in disease prevention.
“The eMERGE Network is well-positioned to advance understanding of the clinical utility of genomics for the prevention of common chronic diseases,” Limdi said. “Conducting a study across multiple conditions, incorporating different types of risk information, although challenging, provides a unique opportunity to clarify study design, define critical endpoints and propose innovative analytical methods to disentangle intervention effects in a real-world setting.”
“Through this work, we are establishing a scalable implementation framework for integrating genomic information into routine care and generating critical evidence on its effectiveness for population risk stratification for the purpose of preventing common chronic diseases.”
UAB authors on this study include Nita Limdi, Pharm.D., Ph.D., Josh Cortopassi, Pharm.D., and Brittney Davis, Pharm.D., Department of Neurology; T. Mark Beasley, Ph.D., and Hemant Tiwari, Department of Biostatistics; James Cimino, M.D., Department of Biomedical Informatics and Data Science; Margurite R. Irvin, Ph.D., Department of Epidemiology; and Bruce Korf, M.D., Ph.D., Department of Genetics.