Accounting for Within- and Between-Locus Dependencies in Marker Association Tests

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dc.contributor.advisor Dennis Boos, Committee Member en_US
dc.contributor.advisor David Dickey, Committee Member en_US
dc.contributor.advisor Dahlia Nielsen, Committee Member en_US
dc.contributor.advisor Bruce S. Weir, Committee Chair en_US
dc.contributor.advisor Russell Wolfinger, Committee Member en_US Czika, Wendy Ann en_US 2010-04-02T18:28:23Z 2010-04-02T18:28:23Z 2003-06-26 en_US
dc.identifier.other etd-03272003-130649 en_US
dc.description.abstract The importance of marker association tests has recently been established for locating disease susceptibility genes in the human genome, attaining finer-scaled maps than the linkage variety of tests through the detection of linkage disequilibrium (LD). Many of these association tests were originally defined for biallelic markers under ideal assumptions, with multiallelic extensions often complicated by the covariance among genotype or allele proportions. The well-established allele and genotype case-control tests based on Pearson chi-square test statistics are exceptions since they adapt easily to multiallelic versions, however each of these has its shortcomings. We demonstrate that the multiallelic trend test is an attractive alternative that lacks these limitations. A formula for marker genotype frequencies that incorporates the coefficients quantifying various disequilibria is presented, accommodating any type of disease model. This enables the simulation of samples for estimating the significance level and calculating sample sizes necessary for achieving a certain level of power. There is a similar complexity in extending the family-based tests of association to markers with more than two alleles. Fortunately, the nonparametric sibling disequilibrium test (SDT) statistic has a natural extension to a quadratic form for multiallelic markers. In the original presentation of the statistic however, information from one of the marker alleles is needlessly discarded. This is necessary for the parametric form of the statistic due to a linear dependency among the statistics for the alleles, but the nonparametric representation eliminates this dependency. We show how a statistic making use of all the allelic information can be formed. Obstacles also arise when multiple loci affect disease susceptibility. In the presence of gene-gene interaction, single-marker tests may be unable to detect an association between individual markers and disease status. We implement and evaluate tree-based methods for the mapping of multiple susceptibility genes. Adjustments to correlated p-values from markers in LD with each other are also examined. This study of epistatic gene models reveals the importance of three-locus disequilibria of which we discuss various statistical tests. en_US
dc.rights 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 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. en_US
dc.subject decision trees en_US
dc.subject mSDT en_US
dc.subject haplotype-based tests en_US
dc.title Accounting for Within- and Between-Locus Dependencies in Marker Association Tests en_US PhD en_US dissertation en_US Statistics en_US

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