Evaluating epistasis in whole-genome association studies is an important challenge in human genetics, as many common diseases are thought to have complex underlying genetic architectures that include small independent effects and interactions between many genes. In this project, I applied a simple bioinformatics approach for generating and ranking biologically supported multi-locus models of multiple sclerosis (MS) susceptibility, using data sources implying interaction of molecules, sources implying gene relationship to disease, and literature-based information. Putative gene-gene interaction models were constructed based on these relationships. These models were evaluated in whole-genome association dataset consisting of 931 MS case/pseudo-control pairs, 2,950 population-based controls, and a replication sample of 808 MS cases and 1,720 controls. Using this approach, I highlight the potential utility of this knowledge-driven analysis technique, and propose a potential role for inositol-based signaling molecules in multiple sclerosis susceptibility.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03052009-112552 |
| Date | 12 March 2009 |
| Creators | Bush, William Scott |
| Contributors | Douglas P. Mortlock, Jay R. Snoddy, James E. Crowe, Jonathan L. Haines, Marylyn D. Ritchie |
| 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-03052009-112552/ |
| Rights | unrestricted, 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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