Batch effects also impacted the power of the two-stage studies (Table 5). The two-stage studies that were based on the larger follow-up platforms were less impacted by batch effects than the studies that were based on the smaller follow-up platforms (the range in power for the 16500 platform was 0.74–0.87 while the range for the 100 platform was 0.70–0.95, before factoring in the impact of the mean systematic inflation of test statistics across the genome). Accounting for systematic batch effects on other SNPs across the genome (which increased the significance threshold in stage 1 required for inclusion of the SNP into stage 2) had near negligible impact on power for the larger follow-up platforms but resulted in small declines in power for the smaller follow-up platforms. Even after factoring in the impact of batch genotype effects, the two-stage study designs typically outperformed the one-stage study design based only on study controls.
