Utilization and Assessment of Ancestry- Informed Genomics in Admixed Populations: Recommendations for Precision Medicine Initiatives

Approximately 50% of adults in the United States have at least one chronic disease, and rates of burden vary greatly among affected individuals. Early diagnosis and intervention of chronic diseases are key features of precision medicine initiatives, which are further complicated by heterogeneity among both risk factors and genetic susceptibility. Despite the development of ancestry-informed genomic analyses, which can be applied to determine ancestry-driven genetic susceptibility for disease risk, there is a lack of heterogeneity in predictive ability effecting both recently admixed and non-admixed groups. Moreover, few genetic studies are positioned to examine the modifying effects of risk factors, which can result in inflated estimates of genetic effect leading to further inaccurate predictive ability. The utilization of ancestry-informed genomic analyses and the integration of ancestry-driven genomic discoveries in precision medicine 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 risk factors in the context of electronic health record data using asthma as a well-characterized and 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 ethical, legal, and social implications. After narrowing my focus to initiatives that lack accurate and precise predictive ability, I will develop and assess a list of priorities related to integrating ancestry-informed genomics into these studies. The proposed studies will greatly 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, known risk factors, and chronic disease. Second, they will provide guidelines and recommendations for implementing ancestry-informed genomics in large-scale clinical settings, creating advancements in predictive ability for precision medicine initiatives. Moreover, the completion of these aims and funding from this award will be imperative to my ultimate goal of building an impactful researcher seeking to break down scientific silos and foster cross-sector collaboration towards comprehensive genomic efforts.