Our conclusions must be tempered by the recognition that our sample was relatively young and almost entirely of European ancestry. In addition, some may view the inclusion of large numbers of only moderate AD cases as a limitation (47). We have argued elsewhere (48), however, that moderate dependence is associated with many substantively important outcomes, including reproductive delay (49), and marital breakdown, family conflict, and adverse environmental exposures including physical and sexual abuse (48). Additionally, moderate dependence is itself an important transition in the progression to severe dependence. What we cannot exclude from our analyses, because of relatively small numbers of severely dependent cases, is the likelihood that additional genetic factors contribute to severe dependence risk above and beyond those associated with heaviness of drinking. In the long term, only the progressive and parallel identification of genes contributing to risk of dependence in community ascertained versus severe clinic samples will clarify this question.
