Our findings extend the current literature, in which the most common approach to defining a phenotype for harmful alcohol consumption has been the diagnosis of alcohol use disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). While this phenotype has clinical utility, it is time-consuming and costly to obtain, substantially limiting large-scale genetic discovery. Although it may also be tempting to use the International Classification of Diseases (ICD) administrative codes as a phenotype for large-scale discovery, these tend to be highly insensitive measures (McGinnis et al., 2010, McGinnis et al., 2013). By first validating a set of AUDIT-C measures against a direct alcohol biomarker (PEth) and then comparing their association with an established molecular genetic factor that is protective against harmful alcohol use, we were able to demonstrate the superiority of AUDIT-C trajectories over both the highest and closest AUDIT-C metrics.
