Cosegregation, in turn, is the expectation that the endophenotype will be more prevalent among the affected relatives compared to the unaffected relatives of ill probands. To date, there have been no animal or human studies of cosegregation patterns for alcohol endophenotypes. Lastly, biological and clinical plausibility refers to the assumption that the endophenotype will bear a conceptual relationship to the disorder of interest. Subjective responses to alcohol are conceptually related to the clinical construct of alcoholism in that individuals who are more sensitive to the rewarding and positive effects of alcohol are thought to crave alcohol more (e.g., consistent with the results in Table 1) and to drink more (Lewis & June, 1990; Wise & Bozarth, 1987), whereas sensitivity to the unpleasant effects of alcohol may deter alcohol use and serve as a protective factor, as discussed below. From a biological standpoint, there is evidence that subjective responses to alcohol are informative regarding neurobiological and genetic factors underlying alcoholism. This evidence will be reviewed in the next sections focusing on pharmacodynamic and pharmacokinetic factors subserving the endophenotype of response to alcohol.
