NIH Funds Research to Understand How Genomics of Diverse Populations Affect Clinical Care

July 10, 2020

Polygenic risk scores, which evaluate disease risk based on DNA variants, have previously been based almost entirely on patients who had European ancestry.

Ten US research centers will receive $61 million over 5 years to develop protocols for evaluating disease risk for diverse populations, based on genomic and environmental factors. The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), announced the awards July 1.

The project, Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network, will build upon work of the existing eMERGE Network, and help these institutions recruit a higher percentage of patients from diverse ethnic backgrounds. The goal is to serve patients who are typically underrepresented in clinical trials or who typically have poor clinical outcomes.

NHGRI funds eMERGE, which brings together DNA biorepositories with electronic health record (EHR) systems to allow high-throughput genetic research to advance personalized medicine. While much of this kind of work is associated with cancer research, eMERGE and the grants awarded in the new round of funding will work to advance protocols that will determine care models for diabetes and cardiovascular disease and determine who is at risk for Alzheimer disease.

The challenge of bringing diversity to clinical trials has been well-documented in the scientific literature in recent years. A 2016 workshop at the European Society of Human Genetics explored the need to address disparities by engaging communities that been historically underrepresented in genomics research; without data from these populations, interpreting genetic testing results would be difficult when these patients sought care, and pathways based on clinical trials might not produce the same outcomes in these populations.

Where the Money Goes

In addition to the $61 million to the 10 sites, $13.4 million will go to the eMERGE Network Coordinating Center at Vanderbilt University.

The 10 sites will be in 2 categories. The first group, to include Mayo Clinic, Rochester, Minnesota; Vanderbilt University Medical Center, Nashville, Tennessee; Brigham and Women’s Hospital, Boston; and Northwestern University, Chicago, will seek 10,000 patients, of which at least 35% should be from underrepresented groups.

The second set of locations, called enhanced diversity clinical sites, will seek 15,000 patients, of which 75% must be from diverse groups. These are the University of Alabama, Birmingham; Icahn School of Medicine at Mount Sinai, New York City; Cincinnati Children's Hospital Medical Center; Columbia University, New York City; Children’s Hospital of Philadelphia; and University of Washington Medical Center, Seattle.

Officials for Children’s Hospital of Philadelphia (CHOP) noted the specific requirements of this round of funding called for enrolling at least 2500 new participants who had not been previously involved with the hospital’s Center for Applied Genomics (CAG), of which 75% must be African American.

“The Center for Applied Genomics and the National Institutes of Health have had an excellent partnership within the eMERGE Network, and we are thrilled to continue to build upon the valuable work that we have been able to achieve so far with particular emphasis on resolving diseases in diverse patient populations and minority groups,” Hakon Hakonarson, MD, PhD, director of the CAG at CHOP and principal investigator of the program, said in a statement. “The primary goals of this program are to identify disease risks faced by patients and their families and to determine the most appropriate actions we can take to improve health outcomes. The program specifically focuses on African American children and their families, who will constitute 75% of participants.”

Polygenic risk scores, which evaluate disease risk based on DNA variants, have previously been based almost entirely on patients who had European ancestry. Investigators have seen a need to incorporate data from patients from non-European ancestry into risk scores, as well as those who have clinical and lifestyle characteristics seen in the real world, such as higher body mass index (BMI), alcohol use, elevated blood glucose levels, and other factors that affect a person’s risk level.

The eMERGE Network, launched in 2007, first collected electronic health record data to address this problem. The sites that will proactively collect data over the next 5 years will add new data to incorporate into risk calculations.

The goal is to develop protocols to estimate risk for common, complex diseases, such as coronary heart disease, diabetes, or Alzheimer’s disease, and incorporate health management recommendations for clinicians into the EHR using the Fast Healthcare Interoperability Resource Standard, which spells out how health information is to be shared electronically.