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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

Authors 

H PaikJ KimS LeeHyoung Sam HeoCheol-Goo HurD Lee

Publisher 

Springer Verlag (Germany)

Issue Date 

2012

Citation 

Molecules and Cells, vol. 33, no. 4, pp. 351-361

Keywords 

genome-wide association studyinteraction networkprioritizationSNP

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.

ISSN 

1016-8478

Link 

http://dx.doi.org/10.1007/s10059-012-2264-7

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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