effect sizes similar to the published examples. Indeed, extrapolation of effect sizes and frequencies from published studies shows (Figure 3) that thousands of individuals are required to reach acceptable statistical power. This analysis is consistent with an earlier study based on population genetic simulations that concluded that as many as 10,000 individuals at phenotypic extremes would be needed to achieve satisfactory power30. The very first GWAS82–84 were also highly underpowered but the combination of falling costs and combining studies in meta-analyses enabled rapid creation of well-powered studies and many discoveries. Similarly, with the falling cost of sequencing and targeted enrichment85, exome sequencing will soon be affordable to many research groups, and we expect that consortia will form to facilitate pooling of exome sequencing data, thus enabling better powered studies and a new wave of discoveries.
