Some methods propose testing GxE interactions at the gene level, rather than the SNP or genetic variant level [Chatterjee, et al. 2006; Lin, et al. 2013]. In these methods, all variants in a gene region are considered as a unit. Although such approaches may focus and reduce the total number of interaction tests being performed, the methods require multiple degree of freedom tests or strong parametric assumptions, which may result in greater loss of power. There is uncertainty in how to define a gene or gene region, leading to uncertainty in what variants to include in these tests [Djebali, et al. 2012]. Furthermore, gene based approaches do not account for variation in intergenic regions.
