has been the exception rather than the rule in GWAS analyses, and only a few small-scale examples are available.27 A search for epistatic effects is computationally demanding, as several billions of SNP pairs exist for typical genotyping chips and gene-environment interactions pose formidable methodological challenges. Recently, several methods and software packages have been developed for the consideration of the statistical interactions between loci26,27 and between genes and environmental factors.28 The application of these methodologies is expected to enhance the power to detect associations and to provide further insight in the biological and biochemical pathways of disease.26 Although the detection and interpretation of these interactions will not be straightforward, genome-wide interaction testing is the next natural step after the single-locus univariate analysis techniques.
