Because the AN GWAS and cannabis initiation GWAS each identified eight significant loci (Pasman et al., 2018, Watson et al., in press), and the two studies comprising the AUD sample identified 10 significant loci (Kranzler et al., 2019, Walters et al., 2018), we also conducted exploratory follow-up MR analyses for AN-AUD and AN-cannabis initiation to examine whether there might be evidence of a causal relationship, given their significant rg. We used summary statistics from a subset of the AN GWAS that did not include the UK Biobank cohort for the AN-cannabis initiation analysis, as this cohort overlapped with the cannabis initiation sample (AN subset without the UK Biobank cohort, Ncases=16,224, Ncontrols=52,460). We did not obtain an estimate for the cannabis inititiation to AN direction of effect because only four SNPs were available after clumping, all of which were excluded for potential pleiotropy by the HEIDI-outlier analysis. There was no evidence of a causal relationship for any comparison (p>0.05; see Supplemental Table 2).
