Large-scale commercial genotyping platforms have facilitated the identification of numerous common single nucleotide polymorphisms (SNPs) that are associated with complex genetic diseases. The high cost of genome-wide association (GWA) studies has lead to the utilization of multi-stage study designs. Two-stage genotyping designs typically involve genotyping a fraction of the entire sample on a commercial genotyping platform containing all SNPs of interest in stage 1, performing systematic tests of association using stage 1 samples, and genotyping stage 2 samples on only the SNPs of greatest interest as determined in stage 1 (Satagopan et al., 2002). Two-stage genotyping designs have been shown to maintain power comparable to a single-stage study employing all samples while substantially decreasing overall genotyping costs (Kraft, 2006;Satagopan et al., 2002;Satagopan et al., 2004;Skol et al., 2006;Skol et al., 2007;Thomas et al., 2004;Wang et al., 2006). The data collected from the second stage of a two-stage GWA study is either analyzed separately as a replication-based sample or the data is combined with data from the first stage and the combined data is analyzed jointly. A recent alternative approach for
