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Open Access Highly Accessed Methodology article

An R package "VariABEL" for genome-wide searching of potentially interacting loci by testing genotypic variance heterogeneity

Maksim V Struchalin1, Najaf Amin1, Paul HC Eilers2, Cornelia M van Duijn1 and Yurii S Aulchenko13*

Author Affiliations

1 Department of Epidemiology, Erasmus MC, Rotterdam, 3000 CA, The Netherlands

2 Department of Biostatistics, Erasmus MC, Rotterdam, 3000 CA, The Netherlands

3 Recombination and Segregation laboratory, Institute of Cytology and Genetics SD RAS, Novosibirsk, 630090, Russia

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BMC Genetics 2012, 13:4  doi:10.1186/1471-2156-13-4

Published: 24 January 2012

Abstract

Background

Hundreds of new loci have been discovered by genome-wide association studies of human traits. These studies mostly focused on associations between single locus and a trait. Interactions between genes and between genes and environmental factors are of interest as they can improve our understanding of the genetic background underlying complex traits. Genome-wide testing of complex genetic models is a computationally demanding task. Moreover, testing of such models leads to multiple comparison problems that reduce the probability of new findings. Assuming that the genetic model underlying a complex trait can include hundreds of genes and environmental factors, testing of these models in genome-wide association studies represent substantial difficulties.

We and Pare with colleagues (2010) developed a method allowing to overcome such difficulties. The method is based on the fact that loci which are involved in interactions can show genotypic variance heterogeneity of a trait. Genome-wide testing of such heterogeneity can be a fast scanning approach which can point to the interacting genetic variants.

Results

In this work we present a new method, SVLM, allowing for variance heterogeneity analysis of imputed genetic variation. Type I error and power of this test are investigated and contracted with these of the Levene's test. We also present an R package, VariABEL, implementing existing and newly developed tests.

Conclusions

Variance heterogeneity analysis is a promising method for detection of potentially interacting loci. New method and software package developed in this work will facilitate such analysis in genome-wide context.

Keywords:
single-nucleotide polymorphisms (SNPs); genome-wide association (GWA); gene-environment interactions (GxE); gene-gene interactions (GxG); variance heterogeneity; environmental sensitivity; VariABEL; the GenABEL project