Findings from genetic association studies such as the current analyses may be sensitive to the specific operationalization of the phenotype. While our measure of dependence symptom count provides greater phenotypic information than would be available from a diagnostic dichotomization of case versus control, future studies of measured genetic influences on substance dependence could potentially benefit by applying phenotype refinement strategies, such as aggregating across informant- and self-report measures (e.g. Achenbach et al. 2005) or including measures of frequency or quantity of use (e.g. Chen & Kandel 2002). By reducing the extent of measurement error in our phenotype of interest, such refinements may provide a way to improve our power to identify genetic associations.
