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Knowledge-Driven Genome-Wide Analysis of Multigenic Interactions Impacting HDL Cholesterol Level

Growing interest and burgeoning technology for discovering genetic mechanisms that influence disease processes have ushered in a flood of genetic association studies over the last decade, yet little heritability in highly studied complex traits has been explained by genetic variation. Non-additive gene-gene interactions, which are not often explored, are thought to be one source of this "missing" heritability. I begin this dissertation with a review of study designs and analytical methods for genetic association studies. Next, I characterize and present a series of improvements in using grammatical evolution to train neural networks for discovering gene-gene interactions in disease gene association studies. I then present an analysis of cis-epistasis - nonadditive multi-SNP interactions that influence gene expression. Next, I present a cohesive set of quality control procedures to be used for genome-wide association studies. Finally, I conclude by presenting results from a knowledge-driven gene-gene interaction analysis of HDL level in two clinical practice-based population biobanks.

Identiferoai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12162010-145118
Date21 December 2010
CreatorsTurner, Stephen Dale
ContributorsDana Crawford, Yu Shyr, Marylyn D. Ritchie, Jonathan Haines, Erik Boczko
PublisherVANDERBILT
Source SetsVanderbilt University Theses
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.library.vanderbilt.edu//available/etd-12162010-145118/
Rightsunrestricted, 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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