The Effects of Admixture on Complex Trait Architecture
Restricted (Penn State Only)
- Author:
- Huang, Jinguo
- Graduate Program:
- Bioinformatics and Genomics (PhD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- August 15, 2024
- Committee Members:
- David Koslicki, Program Head/Chair
George Perry, Major Field Member
Joan Richtsmeier, Outside Field Member
Mark Shriver, Chair & Dissertation Advisor
Zachary Szpiech, Outside Unit Member
Arslan Zaidi, Special Member - Keywords:
- Complex traits
Admixture
Heritability
Polygenic risk prediction
Admixed populations
Population genetics
Statistical genetics
Human genetics - Abstract:
- Admixture is ubiquitous throughout human history and plays an important role in shaping the genetic architecture of complex traits. However, most statistical genetic methods assume random mating. It is unclear how this assumption will affect inferences of the complex trait architecture, such as heritability estimation and polygenic prediction, especially in the presence of population structure and assortative mating. In this dissertation, I focused on the effect of admixture on three properties of complex trait architecture: heritability, ancestry-trait correlation, and polygenic scores, and studied how population stratification would impact heritability estimation and polygenic prediction. In Chapters 2 and 3, using theory and simulation, I found these properties depend on the trait architecture, admixture history, and ancestry-stratified mating. In Chapter 4, I illustrate this empirically using skin pigmentation as a case study. This dissertation provides a theoretical framework to understand the genetic architecture of complex traits in admixed populations, points out the limitations of current statistical genetics methods, and presents an optimistic outlook for the future as genetic and phenotypic data from admixed populations becomes increasingly available.