We recognize several potential limitations of our study. First, the alcohol consumption phenotypes were based on self-reported information, which may result in underestimates of the effects of individual SNPs due to phenotype misclassification. Nonetheless, self-reported measures of alcohol consumption, including drink frequency and regular quantity at the time of heaviest drinking, have been shown to correlate strongly with the genetic risk for alcohol use disorders such as dependence.20 Second, the GERA cohort members are older on average than the general population, which could affect both the generalizability of our findings and our power to observe genetic effects which may be strongest in young adulthood. For instance, older subjects may consume alcohol in a different manner (e.g. better quality of alcoholic beverages, low-risk pattern of drinking while eating) in comparison to younger subjects.16 Further, older subjects may reduce their alcohol consumption due to comorbid conditions or medication use. In addition, participants included in the present study may be healthier and/or more affluent than the general population, as they are all members of the KPNC health plan. We recognize that our restriction
