A characteristic of our sample is a high level of comorbidity with other kinds of substance dependence and ND, a consequence of our recruitment methods and also of our detailed phenotypic assessment protocol. Notwithstanding this fact, we note that we have replicated ND findings first reported by other groups (for example, regarding the CHRNA3/A5/B4 gene cluster (46)), and our findings have been replicated by others (for example, ANKK1/TTC12 ((47-49)). This holds not only for association findings, but for linkage findings as well. Thus, existing evidence supports our hypothesis that ND in this sample is similar to ND in other samples. Of the 33 subjects from the comparison group who carried missense rare variants in the exon 5 cytoplasmic loop region (two of whom had double missense rare variants at different loci), two were alcohol dependent, and one was cocaine dependent. All of the other individuals were healthy, with no psychiatric disorders or substance dependence. All ND cases who carried missense rare variants in the cytoplasmic loop region were comorbid with alcohol, cocaine or opioid dependence.
