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 donât 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.
|Date||21 August 2008|
|Contributors||Daowen Zhang, Trudy F. C. Mackay, Zhao-Bang Zeng, Jung-Ying Tzeng|
|Source Sets||North Carolina State University|
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