Virtually all research conducted on endophenotypes address the threshold criteria in Section I of Table 1. These criteria have provided the default definition of an endophenotype for decades. However, virtually every human trait of significance is heritable (Polderman et al., 2015), so the current threshold for considering any biomarker as a putative endophenotype is low. The proliferation of candidate endophenotypes motivated primarily by meeting these threshold criteria has thus far contributed little to our understanding of the genetics of psychopathology. Given the current state of molecular genetic knowledge and methods, continued reliance on this default definition has outlived its usefulness; it is time to hold the definition of an endophenotype to a higher standard, and require that it demonstrate verifiable association with genetic variants. To achieve this criterion, the work supporting the molecular genetic basis of the endophenotype must be adequately powered, a topic we consider at length in subsequent sections. In addition, any molecular genetic finding must be supported through replication or meta-analysis. Once this is established, conducting investigations to determine if the same variants are associated with the
