On quantitative issues pertaining to the detection of epistatic genetic architectures

Thesis type
(Thesis) M.A.
Date created
2021-01-25
Authors/Contributors
Abstract
Converging empirical evidence portrays epistasis (i.e., gene-gene interaction) as a ubiquitous property of genetic architectures and protagonist in complex trait variability. While researchers employ sophisticated technologies to detect epistasis, the scarcity of robust instances of detection in human populations is striking. To evaluate the empirical issues pertaining to epistatic detection, we analytically characterize the statistical detection problem and elucidate two candidate explanations. The first examines whether population-level manifestations of epistasis arising in nature are small; consequently, for sample-sizes employed in research, the power delivered by detectors may be disadvantageously small. The second considers whether gene-environmental association generates bias in estimates of genotypic values diminishing the power of detection. By simulation study, we adjudicate the merits of both explanations and the power to detect epistasis under four digenic architectures. In agreement with both explanations, our findings implicate small epistatic effect-sizes and gene-environmental association as mechanisms that obscure the detection of epistasis.
Document
Identifier
etd21250
Copyright statement
Copyright is held by the author(s).
Permissions
This thesis may be printed or downloaded for non-commercial research and scholarly purposes.
Supervisor or Senior Supervisor
Thesis advisor: Maraun, Michael D.
Language
English
Member of collection
Attachment Size
input_data\21134\etd21250.pdf 7.03 MB