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Title page for ETD etd-07162014-192116

Type of Document Master's Thesis
Author Wiley, Laura Katherine
URN etd-07162014-192116
Title Discovery and Replication of Pathway-Based Trans-Expression Quantitative Trait Loci
Degree Master of Science
Department Biomedical Informatics
Advisory Committee
Advisor Name Title
William S Bush Committee Chair
Josh F Peterson Committee Member
Joshua C Denny Committee Member
  • trans-eQTL
  • SPIA
  • KEGG
  • gene expression
Date of Defense 2014-06-27
Availability unrestricted
A logical mechanism by which SNPs affect the pathophysiology of disease is through altering the expression of genes. Several studies have explored how SNPs alter expression of nearby genes (cis-eQTLs), but far fewer studies have explored distant effects (trans-eQTLs). This is likely due to the dramatic expansion of statistical tests required and the limited interpretability of results. We hypothesize that distant effects seen in trans-eQTLs are propagated or mediated by biological pathways. To investigate this hypothesis, we performed a focused trans-eQTL analysis on SNPs with known cis-effects by applying Signaling Pathway Impact Analysis (SPIA) to two independent datasets that have both genotype and gene-expression data. Fifteen SNP-Pathway associations were identified and replicated after correction for multiple testing. Given our requirement that all SNPs have cis-effects we performed conditional analyses to determine the effect of the cis-gene expression on our SNP-Pathway associations. Additionally, we annotated these results for functional elements from the ENCODE project to determine biological plausibility and generalizability. In summary, we identify trans-eQTL effects within the context of biological pathways that replicate across multiple ethnic populations.
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