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Analytical tools for population-based association studies

Disease gene fine mapping is an important task in human genetic research. Association analysis is becoming a primary approach for localizing disease loci, especially when abundant SNPs are available due to the well improved genotyping technology during the last decades. Despite the rapid improvement of detection ability, there are many limitations of association strategy. In this dissertation, we focused on three different topics including haplotype similarity based test, association test incorporating genotyping error and simulation tool for large data set. 1) Previous haplotype similarity based tests donĂ¢t have the ability to incorporate covariates in the test. In chapter 2, we proposed a new association method based on haplotype similarity that incorporates covariates and utilizes maximum amount of data information. We found that our method gives power improvement when neither LD nor allele frequency is too low and is comparable under other scenarios. 2) In chapter 3, we proposed a new strategy that incorporates the genotyping uncertainty to assess the association between traits and SNPs. Extensive simulation studies for case-control designs demonstrated that intensity information based association test can reduce the impact induced by genotyping error. 3) In chapter 4, we described simulation software, SimuGeno, which is used to simulate large scale genomic data for case-control association studies.
Date21 August 2008
CreatorsLiu, Youfang
ContributorsDaowen Zhang, Trudy F. C. Mackay, Zhao-Bang Zeng, Jung-Ying Tzeng
Source SetsNorth Carolina State University
Detected LanguageEnglish
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, 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.

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