The completion of the International HapMap Project (1) and the development of advanced genotyping technologies have made genome-wide association studies (GWAS) possible. These studies typically genotype more than 1000 cases and 1000 controls for 300 K to 1 million SNPs. A number of GWAS have been published with many more in progress (2–4). A number of disease-associated SNPs have been identified and confirmed by these breakthrough studies with many more yet to come. Repeating GWAS in additional individuals has helped to find more disease-associated SNPs, although doing so is costly. Interestingly, the SNPs identified and subsequently confirmed in large replication samples are not always those with the smallest P-value in the GWAS, and two GWAS may have radically different P-values assigned to a confirmed SNP. For example, in prostate cancer a confirmed SNP in MSMB from the initial GWAS had a P-value of only 0.042, but the P-value was 7.31 × 10–13 in a follow up study (4,5). Thus the list of potential SNPs from any GWAS remains large. This large SNP list poses a problem for validation studies where a very large number of people are genotyped because custom arrays can cost more than standard GWAS arrays.
