These findings highlight the potential utility of integrating genomic annotation information in order to increase the signal-to-noise ratio in polygenic scores, and identify genetic variants that may be most susceptible to environmental modification. This work can be expanded in several ways, including extensions to jointly consider multiple annotation categories (Pickrell, 2014) and to make use of alternative weighting schemes to up- and down-weight variants across a range of regulatory marks rather than the blunt filtering tool applied here. Such advancements, in conjunction with ongoing efforts to increase power in gene identification studies, have the potential not only to provide biological insights into the etiology of alcohol misuse and other complex psychiatric disorders, but also to one day provide clinical utility to identify and treat at-risk individuals.
