In recent years population-based association studies have been advocated as the most powerful method of discovering genetic loci that are associated with heritable traits, particularly for complex traits that are likely caused by a variety of factors including environmental effects and multiple genetic loci. Genome-wide association studies (GWAS) have already yielded a large number of such associations, but there is growing concern that the results of these studies are not explaining as much genetic variation as they were expected to. Chapter 2 discusses tagging and imputation to leverage the information available on commercial genotyping chips to make inferences about variants found in large reference samples such as those made available by the International HapMap Consortium. Transferability of multi-marker tagging is assessed. Tagging and imputation are compared, and a method of using tagging to select a reduced tag set to be used for imputation. Chapter 3 details how multiple low frequency causal variants can create synthetic associations among more common variants and may be responsible for many of the genome-wide associations that have already been observed. Examples of synthetic associations are demonstrated in congenital deafness and sickle-cell anemia. Chapter 4 examines issues related to combining samples of diverse genetic ancestry for analysis in genetic association studies. Through simulation it is shown that type I error can be controlled and power increased using statistical methods to account for differences in populations.
| Identifer | oai:union.ndltd.org:NCSU/oai:NCSU:etd-11062009-155400 |
| Date | 03 December 2009 |
| Creators | Dickson, Samuel Price |
| Contributors | Greg Gibson, Marie Davidian, David Bird, Matt Nelson, Jung-Ying Tzeng |
| Publisher | NCSU |
| Source Sets | North Carolina State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://www.lib.ncsu.edu/theses/available/etd-11062009-155400/ |
| 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, dis sertation, 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 NC State 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. |
Page generated in 0.0019 seconds