Because the inclusion of genetically at-risk individuals who never initiated cannabis use might have influenced our results, we repeated the primary analyses in the discovery cohort after removing unexposed individuals. Two of the 3 regions identified remained GWS (eTable 1 in the Supplement). The P value for rs143244591 on chromosome 3 improved slightly (P = 1.13 × 10−8, meta-analysis exposed) and was associated at P ≤ .02 in each of the African American subgroups. The signal at rs77378271 in CSMD1 was almost identical (P = 2.95 × 10−8, meta-analysis exposed) and showed association at P < 5.07 × 10−3 in 2 of the 3 European American subgroup and at P = 4.46 × 10−4 in 1 of the African American subgroups. In addition, the block of SNPs in and around PI4K2B became GWS with a consistent effect direction (minor alleles being protective) in every European American and African American population tested and became GWS (minimum P = 2.98 × 10−8, meta-analysis exposed, at rs147170184). The evidence for pleiotropy between CAD and MDD was attenuated substantially (P = .60) after excluding
