PROJECT SUMMARY / ABSTRACT Disease risk prediction that integrates aspects of clinical history, family history, and lifestyle factors is a core tenet of preventive medicine, with genomic risk increasingly being recognized as a component that may enhance the prediction of disease. In addition to strong risk factors in single genes (monogenic risk), polygenic risk scores (PRS) combine the many small effects of variants across the genome to estimate an individual's disease risk. While PRS are poised to enhance risk prediction for common disease, current challenges to clinical implementation include lack of validation in non-European ancestry groups, and barriers to access to leading-edge genomic technology, research, and testing among underserved populations. The eMERGE 4 Network is conducting a study to prospectively enroll 25,000 adults and children across 10 clinical sites in the United States and return an integrated risk report, called the Genome Informed Risk Assessment (GIRA), which incorporates PRS for 10 common conditions with family history, monogenic risk, social and clinical determinants. Using the GIRA to identify individuals at high risk, the Network will assess uptake of preventive health measures and health outcomes. The Mount Sinai Health System (MS) has been selected as an eMERGE 4 enhanced diversity clinical site, where we have recruited 1,520 of our target 2,500 participants, >75% of whom are from medically underserved populations. At the midpoint of the project, in response to some delays in Network recruitment, we have been asked to recruit an additional 175 adult participants beyond our original goal of 2,500. The Specific Aim for this supplement is to expand enrollment of adult participants from diverse communities in New York City. We will accomplish this by 1) continuing targeted outreach, 2) maintaining a presence in primary care clinics across Mount Sinai, 3) engaging physician champions, clinic staff, and practice managers, 4) bringing on additional recruitment sites as needed, 5) extending recruitment through end July 2024, and 6) continuing outreach and engagement efforts to participants and providers. We will extract data on health outcomes from electronic health records, and other data as requested. Upon completion of this aim we will deliver completed surveys, family histories, meta data, and EHR-derived health outcome data for an additional 175 diverse adults from the Mount Sinai Health System to contribute to the research goals of the eMERGE 4 Network, and will work within the eMERGE Network working groups to analyze these data.

PROJECT NARRATIVE (PUBLIC HEALTH RELEVANCE STATEMENT) The eMERGE 4 Network is prospectively enrolling 25,000 adults and children to return integrated monogenic and polygenic risk, family history, and social and clinical determinants in a Genome Informed Risk Assessment for 10 common conditions and assessing the impact on preventive health measures. Mount Sinai Health System is one of 10 eMERGE clinical sites across the United States, with a recruitment goal of 2,500 high diversity participants. At the midpoint of the project, and in response to some delays in Network recruitment, we will expand our enrollment to recruit an additional 175 adult participants.