Demonstrating an association between a candidate endophenotype and a clinical disorder or correlated clinical characteristic is necessary to establish the clinical relevance of the measure, but the measure need not show high sensitivity or specificity because DSM disorders are heterogeneous and overlapping. The value of the endophenotype is not to validate a DSM diagnosis, but to provide a biologically informed alternative avenue to uncover etiological factors relevant to the types of dysfunction those with a diagnosis experience. As Patrick and colleagues have emphasized (Patrick et al., 2013; Yancey, Venables, & Patrick, 2016), it is not reasonable to expect measures of constructs from different domains, such as a psychophysiological variable and a clinical interview assessment, to show more than a modest association, and correlations smaller than .20 are commonplace (W. G. Iacono, 2014b; W G Iacono, 2016). For this reason, relatively large sample investigations are required to quantify accurately the degree to which variance is shared between an endophenotype and an associated clinical phenotype (e.g., an N of 193 is required to have 80% power for detecting a Pearson correlation of .20 as significant at p<.05).
