the time is ripe to adopt the criteria in Table 1 as an aid to further advance the field. It is time to define an endophenotype as a biobehavioral trait that not only identifies genetic liability for a disorder, but one that has demonstrated robust, verifiable association with specific genetic variants that in turn are associated with a clinically relevant behavioral phenotype (as noted in Section II of Table 1). At present, only one electrophysiological variable, resting heart rate, has reached either of these thresholds (see Tables 2, 3, & 7).Endophenotypes are the same as other complex traits in their genetic architecture. There is no compelling evidence that endophenotypes are associated with genetic variants of large effect or that they are substantially different than other complex phenotypes (see Figure 1). They appear to be polygenic traits influenced by many thousands of genetic variants, all contributing small effects. They do not appear to be any better than clinical phenotypes in their 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
