ND, as well as AN and CUD, is related to the relatively modest sample size of those discovery GWAS. A similar non-significant rg was noted for AUD when the Walters et al. (2018) alcohol dependence GWAS was used as the sole source of summary statistics for problem drinking in the current study. Still, there are several other explanations for this divergence in findings. For instance, for tobacco, the highly addictive nature of nicotine may result in convergence in genomic effects on earlier and later stages of smoking (i.e., a much larger proportion of those who ever smoke become dependent compared with the proportion of those who drink alcohol and develop AUD). For cannabis, given its lower addictive potential, we might have expected stronger associations with CUD than cannabis initiation. In addition to the considerably smaller sample size of the CUD GWAS, the association with cannabis initiation could also be attributed to the small number of cohorts in that discovery GWAS that included individuals with a high likelihood of CUD. It is also possible that the relationship between AN and cannabis use is distinct and that earlier, but not later stages of cannabis use are genetically related to liability to AN.
