Level of response (LR) to alcohol is the second candidate endophenotype for AUD to meet many of Gottesman & Gould’s [3] criteria, with the exception that, to our knowledge, there is not evidence that it co-segregates with AUD within families. LR [also known as subjective response to alcohol; 41] is the degree to which a person responds to a specific dose of alcohol or the number of drinks an individual needs to produce specific psychological and motor effects, and is distinct from acquired alcohol tolerance [42]. Low LR is hypothesized to confer risk for AUD because individuals who are less sensitive to alcohol must consume larger quantities of it in order to experience its effects. A program of research led by Schuckit and colleagues demonstrates that low LR is associated with increased alcohol use and problems across multiple samples [43, 42, 44]. As summarized in a recent meta-analysis, populations at risk for AUD, such as individuals with a family history of alcoholism, typically have lower LR compared to other populations [45]. Heritability (h2) estimates for LR are approximately 60% [46, 47].
