These findings add to a growing literature demonstrating that incorporation of functional information about SNPs can advance our understanding of genetic contributions to complex diseases and disorders (Schork et al., 2013, Edwards et al., 2015, Maurano et al., 2012, Finucane et al., 2015). There was minimal loss in predictive power when polygenic scores were limited to variants in DHS regions, which is an encouraging sign that the included variants may be etiologically relevant given their higher a priori probability of having functional consequences. These results also provide some evidence that, like other complex traits (Maurano et al., 2012, Gusev et al., 2014), regulatory mechanisms appear to play a large role in the genetic factors impacting alcohol use outcomes. We should note, however, that the clinical utility of polygenic scoring methods for alcohol problems remains modest: both DHS- and GW- polygenic scores accounted for < 1% of the variance in alcohol dependence symptoms. It was for this reason that we repeated the analyses with height, where there is greater predictive ability associated with polygenic risk scores calculated from large meta-analyses. We were encouraged to find a parallel pattern of results.
