potential to assist gene findingSample size, sample size, sample size. How the electrophysiological variable is operationalized and measured is certainly important, and improving measurement improves reliability and thus statistical power, but the failure of endophenotypes to uncover genes is not due to poor measurement or particular sampling approaches, and improving measurement or sampling from extremes of the population will not overcome the need for very large samples (see Table 3).Candidate gene studies involving endophenotypes have not uncovered verified genetic variants (see Table 6). They should be discouraged in favor of using large sample GWAS studies and GWAS meta-analysis for genetic discovery.Data sharing. Using endophenotypes to discover novel genetic variants will require sample sizes that number in the thousands or more likely in the tens of thousands, sample sizes that will not be attainable unless investigators share data and establish consortia to pool genotyped samples and harmonize measures.Use endophenotypes to understand mechanisms, not to discover genes. It is now clear that large sample studies needed to identify verified genetic variants associated with psychopathology can be obtained by pooling those with a harmonized measure of psychopathology. In this context, a key value of endophenotypes will not be to identify novel genetic associations,
