One argument for the utility of endophenotypes has been that they may aid in gene discovery for clinical outcomes. Previous genome-wide association work by our group suggests that this is not true for common psychophysiological endophenotypes in large community samples (Iacono et al. 2014b; Vrieze et al. 2014c). Another compelling argument for the utility of endophenotypes is that, for a given gene known to be associated with a clinical disorder, an endophenotype may clarify, pinpoint, or suggest causal neurobehavioral mechanisms by which the gene exerts influence on the clinical outcome. Even if endophenotypes can elucidate neurobehavioral etiology in this way, it will require much larger samples than are routinely used for this purpose. The present study of about 4500 individuals, the largest of its kind to date, produced null results across a wide variety of analyses and genotyping technologies. None of the known schizophrenia variants showed a robust association with any of the endophenotypes. One suggestive single-variant result was for an intronic variant in the gene contactin 4 (CNTN4) associated with both antisaccade and P300, although this association did not
