As Table 1 highlights, we do have significant findings. While many could be false positives, they nevertheless emerged against the backdrop of a carefully considered and conservative data analytic approach, thus warranting attention in future investigations. To our knowledge, this work provides the first examination of the possible contribution of rare variants to endophenotype genetics using exome chip and whole-genome sequencing methods. The results suggest that these approaches, like GWAS based on common variants, are also worth pursuing with psychophysiological measures. As Wilhelmsen (2014, this issue) noted, findings based on small effects may have important biological significance and rare variants can readily implicate genomic regions and etiological mechanisms, with especially profound consequences for the families that carry them. As can be seen from our tabled data in the articles and supporting information, we have many effects that, despite not attaining statistical significance, are associated with quite small p values. Almost certainly, some of these are true associations. It will be up to future investigators to coax the signal out of the data by showing that their effects can be corroborated by ours.
