PROJECT SUMMARY The study of African genomes is an urgent, critical need, not only to promote equity but also as a scientific imperative. Prior studies have included mostly individuals from Western, Central, or Southern Africa, and a major gap is the lack of cohorts from East Africa, who likely have unique demographic history, allele frequency spectrum and linkage disequilibrium patterns. The Somalis are a distinct East African population group who have not been part of genomic medicine research initiatives. Due to political instability, many Somalis emigrated to the United States, with the largest number living in Southeast Minnesota. Using a community based participatory research framework to guide efforts, we engaged with the Somali community including tribal elders, imams, and healthcare workers, as well as representative community-based organizations (e.g., Somali Health Advisory Committee, Pamoja Women) and noted the community’s enthusiasm to engage in genomic medicine research. Our proposed research will enable a research partnership with an underserved population of East African origin to establish a genomic medicine research program in this understudied community. We propose the following specific aims: Aim 1. (a) Expand a community based participatory genomic medicine research effort in the Somali community of Southeast Minnesota. We will be guided by a Community Advisory Board with diverse representation; (b) Create a biobank of 1000 Somali individuals that includes plasma, DNA, and RNA. Clinical variables and social determinants of health will be obtained from the electronic health record and surveys. Aim 2. (a) Perform population genetics analyses of whole genome sequencing (30x) data, to investigate the demographic history of the Somali population. We will use a graph genome reference based on African sequences from the Pangenome Consortium, instead of the linear GRCh38, for more accurate variant calling; (b) Use population genetics data to inform construction of polygenic scores for biologically relevant quantitative traits, starting with lipid levels, height, and body mass index. Aim 3. (a) Identify actionable variants in medically relevant genes (ACMG Secondary Findings v3.0) as well as select pharmacogenomic variants; (b) Return actionable results based on input from the community and participant choice and assess near term outcomes. By conducting research in a unique and understudied racial/ethnic group, the proposed work will extend our knowledge of African genomes, help lessen disparities in genomic medicine and provide novel insights that are relevant to diverse populations.