Several limitations must be considered when interpreting our findings. Because our cases were ascertained entirely from New South Wales ORT clinics, generalizability to samples of individuals not currently in treatment or from other areas will need to be demonstrated. Our primary findings emerged after dividing neighborhood controls into subsamples based on history of lifetime drug dependence; thus, replication in other similarly ascertained samples would provide important confirmation. It is possible that population stratification could have contributed to our findings. Cases and control groups primarily included individuals of European ancestry. Although we did observe ethnicity differences, the most substantial were between cases and ATR controls. We conducted PCA prior to each comparison and, when appropriate, included PCs to control for population stratification. Post hoc comparisons of cases to non-dependent neighborhood controls that included four PCs as covariates produced similar results. Another correlated phenotype (e.g., a component of temperament) could be responsible for the current association findings and those previously reported. While this possibility is difficult to exclude, examinations that have incorporated aspects of temperament have produced mixed results.41,48 Despite the considerably
