Whole genome sequences provide an immense amount of information about genomic variation that is only beginning to be tapped in the present article, and we consider the present results preliminary. Nevertheless, the results suggest that hunting for genes associated with complex phenotypes, including complex endophenotypes, will require alternative approaches to those considered here. The present article is the largest and most comprehensive test of genetic association for psychophysiological endophenotypes undertaken to date. The study sample is richly phenotyped and genotyped, but clearly naïve single variant analyses and gene-based tests with nonsynonymous annotation will not be sufficient to discover strong genetic signals in a sample of this size. The results should bring pause to arguments about the utility of endophenotypes, or intermediate phenotypes, to dramatically increase power to detect individual variants or genes associated with them, or with their relevant clinical phenotypes. Of course, it is possible and perhaps likely that some endophenotypes will serve this purpose in samples of this size, but those are not among our 17.
