The effect of genetic ancestry on the genetic architecture of complex traits in admixed populations
Understanding the genetic basis of complex phenotypes is a critical problem in medical and evolutionary genetics. The evolutionary forces of natural selection and demography have shaped patterns of worldwide genetic variation, which in turn have shaped the genetic architecture of human phenotypic variation. Admixed populations, including African Americans and Latinos, have recent ancestry from two or more ancestral groups and are highly underrepresented populations in human genetics research. As a result, the genetic variation that contributes to the genetic architecture of complex traits in these populations has largely been undefined. Here through a combination of data analysis, population genetic modeling and statistical genetics, we further our understanding of admixed populations and highlight the importance of studying diverse populations. First, in a study of bronchodilator drug response (BDR), we identified both population specific and shared genetic variants associated with differences in BDR in African American and Latino children with asthma. Second, in a study of Hispanics/Latinos, we show that admixture has been a dynamic process in the recent history of Mexican Americans, with ancestry proportions changing over time due to a complex mixture of small effects from several population and cultural factors. Finally, we draw attention to the biases and potential for continued health disparities that persist when utilizing genomic prediction based only on large samples of European individuals in Mexican Americans. Through these studies, we improved upon our understanding of the genetic diversity within admixed populations, its effects on human phenotypic diversity, and subsequently our ability to understand genetic contributions to complex traits and disease.