The role of common and rare variants in gene regulation across human tissues
Abstract/Contents
- Abstract
- Interpreting the phenotypic impacts of the millions of variants within each individual's genome is a fundamental, unsolved problem in genetics and medicine. Thus far, efforts to profile this variation have focused on associations with molecular traits like gene expression. These association studies are becoming larger and more commonplace, though they still face major challenges regarding computation, statistical power, and potential biases in the variants they assess. This dissertation details some of the computational and statistical challenges plaguing these associations studies and offers example solutions. Chapter 2 describes a multiple-testing correction procedure for cis-expression quantitative trait locus (cis-eQTL) studies that dramatically reduces computation time while maintaining accuracy and statistical power for regulatory variant discovery. Chapter 3 explains the bias for common variation in cis-eQTL studies and outlines a general method for the discovery of gene expression outliers to detect rare regulatory variants with large effects across many tissues using the Genotype Tissue Expression dataset. Chapter 4 addresses the disadvantages of this method by developing a test for outlier gene expression which accounts for correlation structure and missing data, thereby allowing for detection of tissue-specific effects. Overall, these chapters provide a better understanding of the role of both common and rare variants and their impact on gene expression across human tissues.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Davis, Joe R |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Bustamante, Carlos |
| Primary advisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Bustamante, Carlos |
| Thesis advisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Petrov, Dmitri Alex, 1969- |
| Thesis advisor | Pritchard, Jonathan D |
| Advisor | Petrov, Dmitri Alex, 1969- |
| Advisor | Pritchard, Jonathan D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Joe R. Davis. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Joe Reese Davis III
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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