endophenotypes may be associated with genetic loci of substantially larger effect sizes than any of our 17, although there is little evidence that psychophysiological or imaging-based endophenotypes are associated with larger effects than other complex traits and diseases (Iacono et al. 2016). Despite the fact that our study could not definitively test all candidate endophenotypes in schizophrenia, we suggest that our findings indicate that mechanism studies of the present kind will not be effective in community samples of the size investigated here, because none of the variants known to be associated with clinical outcome has any appreciable association with any of the endophenotypes. Samples of larger sizes with the endophenotypes measured here may yet uncover that these endophenotypes are indeed associated with schizophrenia risk loci, but the question remains whether such findings warrant the expensive in-person laboratory-based procedures required to measure these particular endophenotypes.
