The gene ontology results are suggestive of multiple processes impacting genetic liability to alcohol problems. As described above, immune functioning and fatty acid metabolism are implicated, suggesting that the physiological response to/processing of ethanol is related to alcohol problems. Those findings are complemented by enrichment of ontologies directly related to nervous system functioning, which are more likely to be related to behavioral or cognitive characteristics and processes related to the misuse of alcohol. Additional studies could derive physiology-specific and behavior/cognitive-specific alcohol-related phenotypes for genome-wide studies, the results of which could be compared to determine the extent to which genetic liability overlaps across these processes. Here, the highest factor loadings for the alcohol problems factor score were related to frequency and quantity of alcohol use, but factor loadings onto items related to loss of control and experiencing negative consequences of drinking were also substantial. Thus, our factor score phenotype is capturing risk that is unlikely to be limited to the physiological response to ethanol exposure.
