Ancestry Estimation and Application to the Genetic of Complex Diseases in Human

Understanding the relationship between genotypes and phenotypes is one of the major aims in biology and medicine. An important foundation to understand this relationship is the clear understanding of the pattern of genetic diversity in different human populations and how it correlates with complex genetic diseases. This would facilitate determining why there are differences in susceptibility to common disease among individuals and populations from different continental ancestry groups. In chapter one, I review the critical background for studying the genetics of complex disease. This includes recent studies for ascertaining the genetic structure of human populations using genetic markers, the importance of genetic variations and how it affects the development of specific phenotypes and specific methods to incorporate genetic substructure in association tests. In chapter two, I introduce our ancestry informative markers (AIMs) set for assessing the continental ancestry and admixture proportions in common populations in America. This set of 128 SNPs can correct for populations stratification in admixed population sample sets. In chapter three, I present additional studies validating these AIMs in multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan African, North and South America and Europe. In addition, a subset of this AIM's, which consists of 93 AIM's are effective in identifying the continental subject groups from the Human Genome Diversity Panels. In chapter Four, I present the application of these AIMs to evaluate the association of genetic admixture in African American and Hispanic populations in Women Health Initiative study (WHI) with different measurements of obesity including Body Mass Index (BMI) and Waist-Hip Ratio (WHR). In chapter five, I further present results of the association of genetic admixture in the same populations and different measurements of hypertension. In chapter six, I discuss some perspective and the direction for the future of this research.