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BMC Genetics 2012
An R package "VariABEL" for genome-wide searching of potentially interacting loci by testing genotypic variance heterogeneityKeywords: single-nucleotide polymorphisms (SNPs), genome-wide association (GWA), gene-environment interactions (GxE), gene-gene interactions (GxG), variance heterogeneity, environmental sensitivity, VariABEL, the GenABEL project Abstract: 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.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.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.Genome-wide association studies (GWAS) have been instrumental in identifying genetic variants involved in complex diseases. In GWAS, the relation between a trait of interest and genetic variation (usually a single nuclear polymorphism -- a SNP) is studied by assessing hundreds of thousands of polymorphisms in thousands of individuals. Several hundreds of loci for dozens of complex human diseases and quantitative traits have been discovered using GWAS [1].Though GWASs were successful in finding single loci associated with a trait, complex genetic models which include many interacting loci and environmental factors are of interest as they may help finding new loci and improve our understanding of the genetics of complex traits. A search for genetic interactions by direct analysis, in which all possible genetic models are examined, meets substantial computational and methodological difficulties. When millions of SNPs are considered, which nowadays has become routine in GWAS, testing for interaction for all possible pairwise combinations of SNPs becomes cumbersome requiring parallel computations using hundreds or thous
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