We have performed a series of calculations to evaluate the statistical power of alternative study designs that either includes public controls, study controls or both. We also describe a novel replication-based two-stage design that uses freely available public control data in stage 1, study controls in stage 2 and study cases genotyped in stages 1 and 2. For each study design, we assessed the impact of both systematic ancestry differences between public controls and study samples and batch genotype effects that could occur due to genotyping public controls and study samples at different times on different genotyping platforms. Not surprisingly, the single-stage study design with both public and study controls had the greatest power under all circumstances considered. These results are entirely consistent with previous reports that have shown the negative effects of disease misclassification on power can be overcome by a using large number of unscreened controls (Edwards et al., 2005;Moskvina et al., 2005;Wellcome Trust Case Control Consortium, 2007;Zheng and Tian, 2005). While the single-stage study using only public controls generally had good power when the number of available
