While genetic association studies have been able to elucidate the importance of genetics in human disease outcomes, these studies are limited by the necessity of collecting specifically tailored cohorts and that they frequently only test a single outcome. This focus on a single disease at a time ignores the interconnected nature of both biological pathways and disease phenotypes. My dissertation uses phenome-wide association scans (PheWAS), a method of testing one predictor for association with many disease outcomes, to expand our knowledge of multiple genetic variants and types of genetic variation. We used BioVU, a biobank linked to de-identified electronic medical records (EMRs), to explored a variety of applications for PheWAS. Each chapter presents a project where PheWAS was implemented as a starting point due to a specific hypothesis, before follow-up analyses based on the PheWAS outcome and out existing knowledge of the gene, protein, or variant were performed. The projects presented here begin with the most straight-forward scenario, directly genotyped single SNPs, and progress to imputed deletions before exploring ways to use PheWAS in multi-dimensional studies. In conclusion, I used PheWAS to uncover novel genotype-phenotype associations, and further explored these associations using other data types in the EMR. While PheWAS can be a useful tool for discovering unexpected disease consequences of genetic predictors, using it successfully requires sufficient knowledge of the genetic variation tested to evaluate the biological relevance of association signals
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11212016-090319 |
| Date | 21 November 2016 |
| Creators | Levinson, Rebecca Terrall |
| Contributors | Joshua C Denny, Melinda C Aldrich, Bingshan Li, Douglas P Mortlock, David C Samuels |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11212016-090319/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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