Environment-wide Associations to Disease and Disease-related Phenotypes
Description:... Common diseases arise out of combination of both genetic and environmental influences. Advances in genomic technology have enabled investigators to create hypotheses regarding the contribution of genetic factors at a breathtaking pace. However, the assessment of multiple and specific environmental factors—and their interactions with the genome-- has not. We lack high-throughput analytic methodologies to comprehensively and systematically associate multiple physical and specific environmental factors, or the "envirome", to disease and human health. We claim that the creation of hypotheses regarding the environmental contribution to disease is practicable through high-throughput analytic methods that have been well established in genomics. In the following dissertation, we develop and apply methods to systematically and comprehensively associate specific factors of the envirome with disease states, prioritizing factors for in-depth future study. The current disciplines of studying the environmental determinants of health include toxicology and epidemiology, which operate on molecular and population scales, respectively. This dissertation proposes approaches in both of these disciplines. For example, we have developed a framework to conduct the first "Environment-wide Association Study" (EWAS), systematically associating environmental factors to disease on a population scale. We have applied this framework to investigate type 2 diabetes and heart disease on cohorts that are representative United States population, finding novel and robust associations in diverse and independent cohorts. Given the lack of explained risk resulting from current day genome-wide studies, the time is ripe to usher in a more comprehensive study of the environment, or "enviromics", toward better understanding of multifactorial diseases and their prevention.
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