The gene-wise association analysis of European ancestry summary statistics identified three significant genes (α=2·664 × 10−6): FOXP2 (p=7·31 × 10−8), PDE4B (p=6·66 × 10−7), and ENO4 (p=3·51 × 10−8; appendix p 17, 27). No pathways were significant (appendix p 18). Three genes, NAT6 (amygdala, cortex, frontal cortex), HYAL3 (both adipose tissues, whole blood, cerebellum, frontal cortex, hippocampus, nucleus accumbens, and spinal cord), and IFRD2 (cerebellum) were significantly related to cannabis use disorder through genetically regulated gene expression (appendix pp 18, 28). Connecting SNPs to genes via chromatin interaction data revealed significant associations in adult brain tissue (ten genes), fetal brain tissues (12 genes), iPSC-derived astrocytes (11 genes), and iPSC-derived neurons (eight genes); these genes included HYAL3, ENO4, CHRNA2, and FOXP2 (appendix pp 18, 29).
