| Summary: | 碩士 === 國立交通大學 === 統計學研究所 === 96 === Endophenotype, which involve the same biological pathways as diseases but presumably are closer to the relevant gene action than diagnostic phenotypes, have emerged as an important concept in the genetic studies of complex diseases. Endophenotype-based genetic analysis is more likely to succeed than phenotype-based one in terms of search for the susceptibility genes. The index, proportion of heritability explained (PHE), has been proven useful in identifying potential endophenotypes.
In this report, we use global gene expression as endophenotypes in search for the susceptibility genes underlying asthma, which is a disease caused by complex interactions of genetic and environmental factors. We judge which gene expressions of probe sets are endophenotypes by using the index PHE and do hypothesis test of PHE. For the problem of multiple testing, we utilize the q-value to control for the false discovery rate (FDR) for significance judgment. We also perform genome-wide association tests for each gene expression and compare various genetic properties between gene expressions with and without significant PHE values. At the end, this thesis has (1) evaluated the appropriateness of using global gene expressing as endophenotypes in searching possible phenotype-related genes, (2) examined the overlap between genes identified by the gene-expression-based analysis and genes already identified in the literature, and (3) assessed genetic characteristics of gene expressions that are identified as the endophenotypes.
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