Searching Genome-wide Disease Association Through SNP Data

Taking the advantage of the high-throughput Single Nucleotide Polymorphism (SNP) genotyping technology, Genome-Wide Association Studies (GWASs) are regarded holding promise for unravelling complex relationships between genotype and phenotype. GWASs aim to identify genetic variants associated with disease by assaying and analyzing hundreds of thousands of SNPs. Traditional single-locus-based and two-locus-based methods have been standardized and led to many interesting findings. Recently, a substantial number of GWASs indicate that, for most disorders, joint genetic effects (epistatic interaction) across the whole genome are broadly existing in complex traits. At present, identifying high-order epistatic interactions from GWASs is computationally and methodologically challenging. My dissertation research focuses on the problem of searching genome-wide association with considering three frequently encountered scenarios, i.e. one case one control, multicases multi-controls, and Linkage Disequilibrium (LD) block structure. For the first scenario, we present a simple and fast method, named DCHE, using dynamic clustering. Also, we design two methods, a Bayesian inference based method and a heuristic method, to detect genome-wide multi-locus epistatic interactions on multiple diseases. For the last scenario, we propose a block-based Bayesian approach to model the LD and conditional disease association simultaneously. Experimental results on both synthetic and real GWAS datasets show that the proposed methods improve the detection accuracy of disease-specific associations and lessen the computational cost compared with current popular methods. INDEX WORDS: Algorithm, GWAS, SNP analysis, epistatic interactions, epistasis, clustering, Bayesian Theory, Markov Chain Monte Carlo SEARCHING GENOME-WIDE DISEASE ASSOCIATION THROUGH SNP DATA