An attractive alternative is to work with endophenotypes because ‘endophenotypes represent more defined and quantifiable measures that are envisioned to involve fewer genes, fewer interacting levels and ultimately activation of a single set of neuronal circuits. The fewer the pathways that give rise to an endophenotype, the better the chances of efficiently discovering its genetic and neurobiological underpinnings’ (Gottesman & Gould, 2003). In short, the genetic basis of endophenotypes is assumed to be less complicated than that of their cognate psychiatric illness, their genetic determination is more direct, and, in consequence, they are potentially more tractable to genetic dissection than the disease states themselves. This presumption is made in most papers that seek to document endophenotypes, but has not so far been rigorously tested, due in large part to the paucity of relevant genetic studies. Our aim in this review is to find out whether the genetic basis of endophenotypes is indeed more tractable to genetic dissection than that of psychiatric disease. In order to do so, we need to establish criteria by which to assess whether a phenotype is likely to be genetically tractable.
