Although the approaches described above could be used in a genome-wide context, the enormous cost, computational burden, multiple comparisons penalty, and general absence of prior knowledge about most SNPs pose additional complexities. For main effects of genes, various design and analysis issues have been widely discussed88,89, so the remainder of this Review focuses on the use of GWA data for G×E. Both two-stage genotyping designs and two-step analyses of a single-stage design discussed below could be applied to interaction studies (Box 5). In contrast to the pathway-based approaches in the previous section, these novel techniques are readily applicable to GWA data now.
