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The Effect of Admixture Processes on the Genetic Architecture of Complex Traits

$25,231F31FY2019HGNIH

University Of California, San Francisco, San Francisco CA

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Abstract

Project Summary Understanding the genetic basis of complex phenotypes is a critical problem in medical and evolutionary genetics. The evolutionary forces of natural selection and demography, including migration, have shaped patterns of worldwide genetic variation, which in turn have shaped the genetic architecture of human phenotypic variation. In the United States, population demography has changed immensely over the 20th century as a result of immigration and this will continue to be one of the primary modes of population growth as the US approaches a ?minority-majority? country. Hispanics/Latinos, the largest and fastest growing group, are a genetically heterogeneous population as result of admixture between African, European, and Native American populations. The effect of these large-scale migrations in contributing to shaping genetic variation and subsequently phenotypic variation is unknown. My preliminary data have shown how dynamic the admixture process has been in the US in the last century, demonstrating a crucial need to infer the demographic histories of these individuals. This proposal will use a combination of data analysis, population genetic modeling and statistical genetics to infer the migration histories of US Hispanics/Latinos and leverage their genetic ancestries to elucidate the genetic architecture of complex phenotypes. The long-term aim of this study is to improve our understanding of disease in Hispanic/Latino populations, which will hopefully lead to personalized medicine for a population that has been highly underrepresented in medical genetic studies.

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