Genetics & Genomics

July 1, 2020

VUMC-led network to focus on polygenic risk for common diseases

With the aid of a $75 million, five-year grant renewal, the Electronic Medical Records and Genomics Network (eMERGE) will venture beyond its current focus on monogenic disease to scoring research participants’ relative risk for complex heritable diseases such as cardiovascular disease, chronic kidney disease and type 2 diabetes.

With the aid of a $75 million, five-year grant renewal, the Electronic Medical Records and Genomics Network (eMERGE) will venture beyond its current focus on monogenic disease, that is, diseases inordinately influenced by single genes and single genomic variants, to scoring research participants’ relative risk for complex heritable diseases such as cardiovascular disease, chronic kidney disease and type 2 diabetes.

The new funding was announced today by the National Human Genome Research Institute (NHGRI) at the National Institutes of Health.

Since its start in 2007, with Vanderbilt University Medical Center serving as both a network site and the national coordinating center, eMERGE has been at the forefront of efforts to bring genomics into day-to-day health care. The network combines efforts from leading scientists and medical centers from around the country, who, with the participation of thousands of enrolled patients, are working to advance genomic medicine for people of diverse ancestry.

The grant renewal includes $13.4 million to VUMC for the national coordinating center. Specific funding for network sites was not disclosed in the July 1 announcement.

Network tools and resources include DNA biorepositories and genotyping, electronic health record data linked to genomic data, and, most recently, reporting of individual results to research participants and their health care teams.

For this new phase of work there are 10 network sites in all: VUMC; Mayo Clinic, Rochester, Minnesota; Brigham and Women’s Hospital, Boston; Northwestern University, Chicago; 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; University of Washington Medical Center, Seattle.

In this new phase the network will enroll approximately 25,000 participants for the eMERGE Genomic Risk Assessment and Management (EMERGEgram) program. The goal is to find people at unusually high risk for common diseases using three tools: polygenic risk scoring, which is a method that adds up the often very small effects of thousands of genetic variants; family health history; and the participant’s clinical history.

Besides genotyping technology, tools that will be used in the project include MeTree family history software, developed by Duke University, and REDCap, research data capture software developed by VUMC.

VUMC’s participation as a network site is through the Vanderbilt Genome-Electronic Medical Records Project, led by Dan Roden, MD, Digna Velez Edwards, PhD, MS, and Wei-Qi Wei, PhD, MD.

“We’re out to test the degree to which polygenic risk, along with other measurable risk, can aid prevention and early treatment of common complex diseases,” said Roden, senior vice-president for personalized medicine. “We believe strongly that data science efforts like eMERGE will transform health care.”

For coordination of the network, VUMC will be joined by Broad Institute of MIT and Harvard, with additional expertise from Duke University.

Leaders for the eMERGE Genomic Risk Assessment Coordinating Center are, for VUMC, Josh Peterson, MD, MPH, professor of Biomedical Informatics, and for Broad Institute, Niall Lennon, PhD, senior director of translational genomics.

“With polygenic risk-scoring being so new, everyone has recognized that implementation into clinical practice is ambitious and will challenge our front-line clinicians,” Peterson said. “In the past, that level of ambition has driven innovation within eMERGE to be one of the first networks to integrate sequencing results into electronic health records at scale.”

While polygenic risk scores don’t yet come with standard guidelines for directing care, “this phase of eMERGE will advance our understanding of how to incorporate these risks into preventive care and surveillance practices,” Peterson said.

Since 2007, eMERGE has accumulated dense phenotypic and genomic data from some 105,000 eMERGE participants, and this data will now be gathered in a cloud-computing repository, providing a secure, centralized, open-ended platform for genomic medicine research.

For more information visit the eMERGE website.