Title
Gene-Gene Interactions Detection Using a Two-stage Model.
Abstract
Genome-wide association studies (GWAS) have discovered numerous loci involved in genetic traits. Virtually all studies have reported associations between individual single nucleotide polymorphisms (SNPs) and traits. However, it is likely that complex traits are influenced by interaction of multiple SNPs. One approach to detect interactions of SNPs is the brute force approach which performs a pairwise association test between a trait and each pair of SNPs. The brute force approach is often computationally infeasible because of the large number of SNPs collected in current GWAS studies. We propose a two-stage model, Threshold-based Efficient Pairwise Association Approach (TEPAA), to reduce the number of tests needed while maintaining almost identical power to the brute force approach. In the first stage, our method performs the single marker test on all SNPs and selects a subset of SNPs that achieve a certain significance threshold. In the second stage, we perform a pairwise association test between traits and pairs of the SNPs selected from the first stage. The key insight of our approach is that we derive the joint distribution between the association statistics of a single SNP and the association statistics of pairs of SNPs. This joint distribution allows us to provide guarantees that the statistical power of our approach will closely approximate the brute force approach. We applied our approach to the Northern Finland Birth Cohort data and achieved 63 times speedup while maintaining 99% of the power of the brute force approach.
Year
DOI
Venue
2014
10.1089/cmb.2014.0163
JOURNAL OF COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
epistasis,gene-gene interaction,GWAS
Data mining,Pairwise comparison,Joint probability distribution,Biology,Genome-wide association study,Single-nucleotide polymorphism,Minor allele frequency,Bioinformatics,Genetics,Locus (genetics),Statistical power,SNP
Conference
Volume
Issue
ISSN
22.0
6
1066-5277
Citations 
PageRank 
References 
0
0.34
6
Authors
5
Name
Order
Citations
PageRank
Zhanyong Wang1507.04
Jae Hoon Sul2223.07
Sagi Snir326327.92
José A. Lozano42148167.25
Eleazar Eskin51790170.53