Polygenic Risk Scores for Healthier African American Families

Abstract eMERGE is a national network organized and funded by the National Human Genome Research Institute (NHGRI) that combines DNA biorepositories with electronic health record (EHR) systems for large scale, high-throughput genetic research in support of implementing genomic medicine. In 2020, eMERGE IV embarked on a study of genomic risk assessment and management in 5,000 children and 20,000 adults of diverse ancestry, beginning with efforts to identify and validate published PRSs in ten common diseases with complex genetic etiologies. The study recruited and returned results to nearly 25,000 individuals (aged 3–75 years) from general healthcare system populations. Enrollment was not targeted to individuals with specific conditions, although individuals with prevalent conditions were included. For this prospective, cohort study, the primary outcome being measured is the number of new healthcare actions after return of the genome- informed risk assessment. Cincinnati Children’s has been an active and engaged site in eMERGE IV. We enrolled participants, completed GIRA returns to participants and their EHRs, surveyed providers, implemented 6-month participant post return of results surveys, and reconsented pediatric participants who turned 18 and. In partnership with another site, we conducted a qualitative study to understand parents’ responses to their children’s PRS-based genomic risk results. Our site has provided Network leadership, and we have been deeply engaged with the other sites and network leadership throughout the study. In this proposal we request a one year extension of funding. During this time, we will perform 6- and 12-month EHR data pulls. We will engage in participant retention strategies as permitted by sIRB protocol. We will complete 6-month participant post-return of result surveys. As needed, we will contribute CCHMC/UC data to existing R4 instruments (and likely new R4 instruments) to assure needed CDP data is available for Network manuscripts. Moreover, we will lead and publish network wide manuscripts as described in the approach. Altogether, we intend to work with the NHGRI leadership and other sites to continue to discover and publish the learnings from the eMERGE IV prospective, pragmatic study following the plans for an extension year that we collaboratively designed as a network.