populations. The 2 African American–specific SNPs were rare or monomorphic in European American participants. The lack of association in European American participants could be owing to different linkage disequilibrium patterns or the absence of causal variants. The Yale-Penn samples who underwent genotyping on the HumanOmni1-Quad and Human Core Exome chips showed more consistent results than the corresponding SAGE population, which is not surprising insofar as SAGE participants were recruited from different areas and ascertained using different criteria (AD, CD, and OD in Yale-Penn and primarily AD and ND in SAGE). The difference in ascertainment criteria (use of licit vs illicit drugs) across studies likely explains the fact that the proportion of cannabis-exposed individuals varied significantly across cohorts (2293 in SAGE population [76.9%] and 7626 in the Yale-Penn population [85.0%]). The limitations of phenotypic distribution and population differences are more relevant to the Australian ICGHD replication cohort and may explain the lack of replication in this cohort. Despite this, we obtained statistically significant evidence for formal replication for the SNP in SLC35G1 and stronger evidence for association at many of the top SNPs after including the replication samples. Finally, these cohorts have higher rates of polysubstance dependence than the general population
