The two-stage genotyping design90 has been extended to GWA scale91-94 and used to discover main effects in many studies. The design is also attractive for GEWIS, but requires choices about how to select the SNPs to be carried forward to the second stage based on promising main effects and interactions. Any SNP for which the main effect or any of the G×E/G×G interaction tests attained the appropriately Bonferroni-corrected significance level would be chosen for inclusion in stage 2 genotyping. While an optimal selection of numbers of hits of each type to pursue so as to maximize the yield of true positives would require knowledge of the distribution of true effect sizes of each type, reasonable bets might be made based on previous literature and calculation of the power to detect similar effects.
