The two phenotypes used in this study were both aggregate measures of overall dependence. Although their top genetic signals did not overlap (i.e. the same SNP did not reach statistical significance for both phenotypes), there was evidence of association for the other phenotype for the two SNPs that attained genomewide significance (see Supplemental Table 1 for additional comparisons). The difference in magnitude of p-value is not surprising given the arguable validity of the diagnostic cutoff (i.e. 3 or more of 7 dependence criteria) implemented in DSM-IV which likely excluded from affected status (for ANYDEP), a number of individuals who may have met criteria for abuse or endorsed 1-2 dependence symptoms across one or even multiple drugs, and thus did not qualify for dependence. Viewed alternatively, the unaffected individuals for ANYDEP represent a heterogeneous group varying in severity. Such variability was better captured by QUANTDEP, which while not taking abuse criteria into account, was a better approximation of the range of vulnerability to substance-related problems. Thus, it is likely that ANYDEP reflects the more severe of the QUANTDEP scores. Finally, the possibility that our findings reflect false positives cannot be excluded.
