PROJECT SUMMARY/ABSTRACT Approximately 50% of adults in the United States have at least one chronic disease, and minority populations have a disparate burden compared to individuals of non-minoritized racial identities. Early diagnosis and intervention are key features of precision medicine initatives, which must first overcome heterogeneity among risk factors, including sex differences and social determinants of health. Despite the development of ancestry- informed genomic analyses, which can be applied to determine ancestry-driven genetic susceptibility for disease risk in diverse populations, recently admixed individuals of African ancestry are underrepresented in genetic studies targeted to identify risk factors for chronic disease. Moreover, few genetic studies are positioned to examine the modifying effects of social determinants of health on genetic risk for chronic disease, which can result in inflated estimates of genetic effect and thus further impinge on precision medicine initiatives in recently admixed individuals of African ancestry. The utilization of ancestry-informed genomic analyses and integration of ancestry-driven genomic discoveries in precision medicine initiatives is paramount for the accuracy and innovation in treating chronic disease. This proposal details the ways in which I, Ms. Kimberlyn Ellis, will fill these detrimental gaps through my doctoral and anticipated postdoctoral research. In Specific Aim 1 (The Dissertation Research Project), I will investigate the interactions between genetic variation, genetic ancestry, and known social and structural risk factors in the context of electronic health record data using asthma as a well-characterized and comprehensive proof-of-principle chronic disease phenotype. In Specific Aim 2 (The Postdoctoral Research Direction), I will conduct a landscape analysis of current genomic-driven precision medicine initiatives, including the ethical, legal, and social implications of the current inequalities. After narrowing my focus to the initiatives that are most disparate for non-European populations, I will develop and assess a list of policy priorities related to integrating ancestry-informed genomics into these initiatives. The proposed studies will greatly diversify and advance the field of genomics in two important ways. First, they will provide a rigorous framework for elucidating the poorly understood relationships between genetic ancestry, social determinants of health, and chronic disease for recently admixed populations with African ancestry. Second, they will provide guidelines and recommendations for implementing ancestry-informed genomics in large-scale clinical settings, creating just and equitable precision medicine advancements for underrepresented groups. Moreover, the completion of these aims and funding from this award will be imperative to my ultimate goal of building an impactful career as an independent researcher seeking to break down scientific silos and foster ...