Some commentaries raised concerns about how the endophenotypes were operationally defined, measured, and analyzed. As Baker (2014, this issue) noted, our endophenotypes could be profitably recast, using multivariate modeling, in a way that facilitates identifying shared genetic influences across measures and phenotypes, possibly including DSM clinical phenotypes. Bivariate analyses of endophenotype and associated trait or disorder provide an opportunity to converge on the genetic overlap between the two, which is certain to be small in magnitude. Focusing on P3 amplitude, Ford (2014, this issue) presented a wealth of creative ideas intended to improve the genetic yield by enhancing reliability and heritability as well as parsing P3 amplitude into components that may prove more genetically tractable (providing “endophenotypes for endophenotypes”; see Miller & Rockstroh, 2013). These are worthy goals, and their implementation could lead to the identification of some associated SNPs, perhaps uncovering important genetic clues that were missed.
