Based on effect sizes and linkage disequilibrium from the case-control European ancestry meta-analysis (cases 14 080, controls 343 726), the genome-wide significant locus on chromosome 8 contains a single association (independent at R2<0·1) with lead SNP rs4732724 (odds ratio [OR] 0·89, 95% CI 0·86–0·93, SE 0·02; p=6·46 × 10−9; figure 1, appendix pp 21–23). This locus was previously associated with cannabis use disorder in the iPSYCH sample3 and includes eQTLs for CHRNA2 (cholinergic receptor nicotinic α2 subunit) in the cerebellum and cerebellar hemisphere and EPHX2 (epoxide hydrolase 2) in the cerebellum and adipose tissue. One genome-wide significant variant in the chromosome 8 locus (rs1565735) had a CADD score of 13·28, indicating high probability of deleteriousness (appendix p 17). There were additional eQTL signals at this chromosome 8 locus, for CCDC25 (coiled-coil domain containing 25, in nucleus accumbens, multiple SNPs), CLU (clusterin, in adipose, rs2640724), and STMN4 (stathmin 4, in prefrontal cortex, rs78875955 and rs72477506; appendix p 25).
