Flint and Munafo noted that the “endophenotypes” that have been used in studies of different psychiatric diseases typically fell into six categories: anatomical, developmental, electrophysiological, metabolic, sensory, and psychological/cognitive [19], providing a useful framework for classifying potential endophenotypes. We adopted this framework to organize the evidence for a number of AUD candidate endophenotypes according to each of the five Gottesman & Gould [3] criteria (Table 1) as well as genes, regions of interest, and gene sets associated with candidate endophenotypes (summarized in Table 2 and visualized as part of a gene-environment interplay system in Figure 1). We also added a “functional neuroimaging” category in view of the growing number of functional brain candidate endophenotypes for AUD [13]. As Table 1 illustrates, the evidence for many of the strict endophenotype criteria is sparse at present. The two candidate AUD endophenotypes for which there is the greatest evidence, and which have generated the most genetic associations, are neurophysiological phenotypes and level of response to alcohol [for detailed reviews of these as candidate endophenotypes, see 8, 12].
