By including multidimensional polygenic scores, we were able to obtain greater insight into the breadth and specificity of genetic effects. PGSs indexing EXT and Problems were broadly associated with average consumption frequency/quantity as well as heavy (episodic) drinking, while Consumption and BeerPref PGSs were more specifically associated with average frequency or heavy drinking, respectively. BeerPref was even inversely related to consumption frequency in some samples, supporting the hypothesis that this construct represents a genetic predisposition involving a low level of response to alcohol that prompts heavier drinking quantity (40), rather than the social influences that are more relevant to drinking frequency (27). Further, different factors appeared to be most relevant across samples, with, for example, only Consumption PGSs showing associations with mean AUBs in the COGA sample but only EXT PGSs being associated with mean AUBs in S4S. This heterogeneity across samples further challenges efforts to pinpoint biological mechanisms or improve genetic risk prediction. Our results highlight the need for genetic studies of the diverse heritable risk processes, both broad and specific, that are important for AUBs.
