VARIANCE HETEROGENEITY IN GENETIC MAPPING Public Deposited

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  • March 21, 2019
Creator
  • Corty, Robert
    • Affiliation: School of Medicine, Curriculum in Bioinformatics and Computational Biology
Abstract
  • Genetic mapping is a process by which researchers seek to identify genetic factors that influence a trait of interest. Such efforts typically focus on those that either increase or decrease the trait of interest, and assume that the variance of the trait is constant across all individuals. I develop and apply statistical methods that challenge that assumption in two ways. First, I consider the situation where non-genetic factors influence trait variance, which I term “background variance heterogeneity”. Though they are not of immediate interest in a genetic mapping study, they can be exploited to align observations’ weights with their precisions. Second, I consider the situation where genetic factors influence trait variance, which I term “foreground variance heterogeneity”. Such factors are of immediate interest because they represent novel discoveries that could be missed by standard analyses. I consider both foreground and background variance heterogeneity as they relate to linkage disequilibrium mapping in exchangeable mapping populations. I report three novel genetic factors with strong evidence that they influence medically-important traits in the mouse model system. Finally, I consider the background variance heterogeneity as it relates to association mapping in non-exchangeable populations. I report a mathematical advance that makes possible the fitting of a statistical model that accommodates background variance heterogeneity in non-exchangeable populations.
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Rights statement
  • In Copyright
Advisor
  • Pardo Manuel de Villena, Fernando
  • Evans, James
  • Li, Yun
  • Valdar, William
  • Tarantino, Lisa
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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