The vast majority of molecular genetic studies of putative endophenotypes have been candidate gene studies with small samples. The performance of candidate gene studies for complex traits in the past decade gives us little reason to believe that their results are verifiable. Nevertheless, we review in this section all studies, whether candidate gene studies or GWAS, with a sample size of at least 400 or that included a replication sample in the original report. This criterion includes studies with a discovery and replication sample as well as the few studies that combined GWAS results across multiple independent samples through meta-analysis. We chose 400 subjects as a minimum sample size because it provides 80% power to detect effects accounting for 2% of the variance in an endophenotype. As we outlined earlier, effect sizes of this magnitude are substantially larger than we expect of true effect sizes, and this targeted minimum sample size should not be taken as a recommendation. It simply allows us to highlight studies that stand out from the majority of molecular genetic studies because they are more highly, although not sufficiently, powered.
