We calculated power for a GWA scan on M = 500,000 SNPs based on a study sample of NA = 2,000 study cases and NU = 2,000 study controls to demonstrate the difference in power between the competing approaches. We assumed a multiplicative model with a GRR = 1.3, and a susceptibility allele frequency fD = 0.3 in the general population. We considered a wide range of disease prevalence values of K = 1×10−4, 0.01, 0.05, 0.1, 0.25, and 0.5 and we assumed available genotype data on samples of NPU = 2,000, 5,000 and 10,000 public controls. We calculated power for the single-stage designs (using only study controls, only public controls, or both control samples combined) and for the optimal replication-based two-stage design. For each optimal two-stage model we provided the power estimate from the follow-up platform that provided the greatest power. Finally, in order to test how power of the 2-stage designs for the four proposed follow-up platforms were impacted by different combinations of susceptibility allele frequency and GRR, we calculated power with K =0.10 (assuming NPU = 5,000)
