PROJECT SUMMARY The Electronic Medical Records and Genomics (eMERGE) Network has been at the forefront of genomic medicine research since its establishment in 2007 and has informed national and international research programs, including the All of Us Research Program. Integral to the Network's success is Vanderbilt's longstanding role as a dedicated Coordinating Center (CC). With Vanderbilt as a founding member, eMERGE pioneered the use of large scale genomic and electronic health record (EHR) data for research, developed and validated over 60 electronic phenotypes, integrated clinically actionable genomic data into the EHR, published over 600 manuscripts, and formed a cohort of over 135,000 adult and pediatric participants that is broadly accessible for further discovery. The next phase of eMERGE will develop and return genomic risk assessments (GRA) in diverse populations, utilizing polygenic risk scores (PRS) to predict and manage the risk of common, complex diseases. We are proposing to form the Genomic Risk Assessment Coordinating center for eMERGE (GRACE) with the Broad Institute to add expertise in large-scale genotyping, cloud computing, and genomic data analysis and management, and with Duke University to leverage its proficiency in the implementation of patient-oriented family history tools and delivery of risk assessments. To meet the needs of the Network, GRACE will continue to serve NHGRI, the Network, and its members in all coordination, communication, and collaboration functions while providing a nationally visible home for eMERGE authored tools and scientific productivity. Secondly, we will assist the Network with selecting and validating polygenic risk scores (PRS) for approximately fifteen complex diseases and developing genomic risk assessments (GRAs) which combine the PRS with other clinical risks, family history, and monogenic risks to individuals of diverse ancestry. Finally, we will coordinate a prospective study for 20,000 participants which calculates clinical and genomic risks for participants and their providers. In addition to providing the genotyping and PRS reporting services, we will develop with the Network scalable EHR-based methods to assess uptake of risk-reduction recommendations and clinical impact.

PROJECT NARRATIVE The Genomic Risk Assessment Coordinating center for eMERGE (GRACE) will create infrastructure to implement and evaluate genomic risk assessments for common, complex diseases such as heart disease, and return these assessments to participants. GRACE will organize collaboration among eMERGE investigators, streamline data collection, and utilize cloud computing to enable large scale analyses of genomic data. GRACE will support the recruitment and genotyping of a 20,000 person cohort to determine the clinical impact of delivering genomic risk assessments, measure the uptake of risk reduction recommendations, and assess changes to clinical outcomes.