Our analyses included several important limitations. First, they were limited to GWAS of European ancestries. Unfortunately, Genomic SEM requires larger sample sizes to obtain stable estimates. As larger sample sizes become available in non-European ancestries, we will extend these models to those populations. Genetic research in diverse ancestries is important scientifically, but also morally, as failure to diversify genetic discovery will result in the exacerbation of health disparities [39]. Second, while we considered externalizing phenotypes, we did not consider internalizing or psychotic conditions, which also show genetic overlap with AUD and other substance use disorders [4, 6, 18, 40, 41]. Finally, our estimates of SNPs associated with ALCP-specific were limited by the relatively small discovery sample size for ALCP-total (N ~ 150 K). We do note that our GWAS of ALCP-total was highly correlated with the largest meta-analysis of problematic alcohol use to date (rG = 0.94, p = 4.94 × 10–324) [3]. Future iterations with more powerful GWAS of problematic alcohol use may reveal additional variants associated specifically with ALCP. Additionally, including traits related to alcohol-specific biological processes may further help distinguish alcohol-specific from other processes through which AUD develops.
