Our analysis of P3 endophenotype-specific candidate genes, which produced null results for P3 recorded at parietal leads, included genes identified in prior GWAS using an oddball event-related potential protocol (Kang et al., 2012; Zlojutro et al., 2011). However, the identified genes were associated with a time-frequency component of frontal theta power associated with the P3 event-related potential. Had we included this same measure, perhaps we would have affirmed these results. However, using MTFS samples, we found that the time-frequency constituent components of P3 are strongly correlated with the time-domain P3 amplitude measure we used (Gilmore, Malone, Bernat, & Iacono, 2010; Gilmore, Malone, & Iacono, 2010; Yoon, Malone, Burwell, Bernat, & Iacono, 2013). Moreover, in MTFS twins, P3 and its time-frequency components show stronger association with the clinical phenotypes in the externalizing spectrum when measured at parietal as opposed to frontal sites (Yoon et al., 2013). Thus, considering the consistency in our findings across many measures, it becomes difficult to resist the notion that, to borrow from Gertrude Stein, there is not much “there there,” and thus little reason to expect further refinement of the endophenotype to lead to valid genetic associations.
