Prioritization of SNPs for genome-wide association studies using an interaction model of genetic variation, gene expression, and trait variation

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Title
Prioritization of SNPs for genome-wide association studies using an interaction model of genetic variation, gene expression, and trait variation
Author(s)
H Paik; J Kim; S Lee; Hyoung Sam Heo; Cheol-Goo Hur; D Lee
Bibliographic Citation
Molecules and Cells, vol. 33, no. 4, pp. 351-361
Publication Year
2012
Abstract
The identification of true causal loci to unravel the statistical evidence of genotype-phenotype correlations and the biological relevance of selected single-nucleotide polymorphisms (SNPs) is a challenging issue in genome-wide association studies (GWAS). Here, we introduced a novel method for the prioritization of SNPs based on p-values from GWAS. The method uses functional evidence from populations, including phenotype-associated gene expressions. Based on the concept of genetic interactions, such as perturbation of gene expression by genetic variation, phenotype and gene expression related SNPs were prioritized by adjusting the p-values of SNPs. We applied our method to GWAS data related to drug-induced cytotoxicity. Then, we prioritized loci that potentially play a role in druginduced cytotoxicity. By generating an interaction model, our approach allowed us not only to identify causal loci, but also to find intermediate nodes that regulate the flow of information among causal loci, perturbed gene expression, and resulting phenotypic variation.
Keyword
genome-wide association studyinteraction networkprioritizationSNP
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.1007/s10059-012-2264-7
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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