Project Summary / Abstract Advances in learning health systems (LHS) and implementation science have great potential to address barriers to equitable genetic medicine. We bring together 4 MPIs and a team of investigators with expertise in learning health systems; implementation science; and cardiovascular and cancer genetic medicine to advance our Northwestern genetics-enabled learning health system (Northwestern gLHS). We will design, implement, and continuously refine strategies to enhance equitable genetic medicine among diverse populations. We are ideally suited to conduct this work for the following reasons. First, Northwestern is a leader in developing an LHS with equity-focused systems solutions that are continuously refined to improve both healthcare delivery and health outcomes. Northwestern's established LHS resources and expertise will support our clinical site and the national gLHS network. These resources and expertise integrate our robust clinical, genetic, and patient-reported data capabilities, institutional and community-based electronic health records, and novel web-based tools and technologies to fully realize the promise of the gLHS. Second, Northwestern is a leader in genetic medicine as a member of the Electronic Medical Records and Genomics (eMERGE) consortium and has recruited and effectively integrated genetic results into Northwestern's EHR as discrete, computable lab values enabling effective clinical decision support. Third, Northwestern's recent investment in senior implementation scientists, coupled with an established environment of community partnership with AllianceChicago, a network of federally qualified health centers, and Alliance for Research in Chicagoland, a network of community-based non-profit agencies, is poised to lead in implementing and disseminating genetics-enabled healthcare. Our Specific Aims include: 1. Bring together our expertise in learning health systems, implementation science, and genetic medicine to advance our Northwestern gLHS to accelerate the equitable impact of emerging genetic evidence in real- world clinical settings within our health system and community settings. 2. Collaborate with the national network to co-design, implement, and evaluate harmonized projects to create generalizable knowledge that accelerates genetic-based equitable healthcare and improved health outcomes. We propose 3 projects on cascade genetic testing (CGT) for hereditary conditions within cardiovascular disease and cancer as our use case. Our proposed projects each address a different aspect of a primary barrier in CGT, over-reliance on probands to transmit the importance of CGT to family members. 3. Develop and disseminate gLHS methods to ensure our learnings with regard to equitable evidence-based genetic medicine can be scaled across real-world healthcare settings. The Northwestern gLHS methods and tools will guide future wide-scale implementation of CGT and other evidence- based genetics practices within health systems and the community while answering important questions related to equitable implementation of genetic medicine to improve health for all.

Project Narrative The Northwestern genetics-enabled learning health system (Northwestern gLHS) brings together a team of investigators with expertise in learning health systems, implementation science, and cardiovascular and cancer genetics. We will design, implement, and continuously refine strategies and resources to enhance equitable genetic medicine among diverse populations. We propose 3 projects on cascade genetic testing (CGT) for hereditary conditions within cardiovascular disease and cancer as our use case to address different aspects of a primary barrier in CGT, overreliance on probands to transmit the importance of CGT to family members.