in frequency of consumption (Frequency Residual) that is unrelated to other AUDIT items. These analyses revealed that Frequency Residual had consistently positive associations with measures of socioeconomic status and consistently negative associations with measures of substance use and psychopathology. Indeed, these genetic correlations are very similar to those observed in GWASs of AUDIT-C (4, 5) and other GWASs of alcohol consumption (3, 4), suggesting that single-item frequency-based measures of alcohol consumption may be particularly susceptible to confounding and/or selection bias. For example, Marees and colleagues (38) reported that greater frequency of alcohol consumption was associated with higher socioeconomic status and lower risk of other psychiatric and substance use disorders in UK Biobank. In population-based cohorts with a “healthy volunteer” bias, such as the UK Biobank, the relationship between frequency of alcohol consumption and aspects of physical and mental health may not be fully generalizable (39). This degree of bias, we speculate, will likely vary from population to population.
