The impact of natural selection and population structure on human genomic variation

Project Summary A key goal of evolutionary biology and human genetics is to understand the ways in which natural selection has shaped genetic and phenotypic variation within and among populations. The vast amount of population-genomic data, ancient DNA sequence data, and genotype-phenotype mapping data being generated bring an unprecedented power to address long-standing questions about the impact of adaptation in human evolution and the role of migration and selection in driving genome-wide evolutionary change. Our lab brings new tools from the intersection of population genetics and statistics to address these questions, capitalizing on a range of new approaches, from building genomic predictions of traits to the construction of genome-wide evolutionary genealogies. To maximize the potential of these new data and approaches, we propose to develop novel population-genomic models and statistical tools that address the roles of natural selection and population structure in shaping population-genomic variation. Specifically, the proposed work will: 1) Estimate the contribution of selection and genetic drift to genome-wide change over a range of different time-scales; 2) Using genome- wide genealogies to estimate recent histories of dispersal and selection; 3) Decompose the sources of confounding in polygenic scores and explore how we can best leverage family-based studies to place GWAS on a more solid conceptual footing. The results of these projects will address fundamental questions about the structure of human genomic variation.