Gene-Environmental Interaction Assessment in Genome Wide Association Study

Abstract

This thesis aimed to investigate congestive heart failure (CHF) associated with anthracycline exposures among the childhood cancer survivors, trying to identify differential anthracycline effects by genotype of certain genes. We had 130 childhood cancer survivors who developed CHF as cases and 269 individually-matched controls. We assessed each single nucleotide polymorphism’s (SNP) interaction with anthracycline dose on the case-control status of CHF. Besides the single SNP analysis, we developed a method that considered SNPs from the same gene as a set and assessed the set’s effect on anthracycline toxicity by extending a gene-set analysis method developed previously for gene expression studies. Some SNPs had interactions with anthracycline exposure on the development of CHF. Moreover, there was stronger evidence from the SNP-set analysis indicated that the interaction between certain sets of SNPs (genes) and anthracycline exist.