As the correlation between consumption measures and dependence is derived from composite phenotypes (e.g., alcohol dependence diagnosis using structured interviews or clinician reports, consumption via self-reports) and in heterogeneous samples, further work is needed to pinpoint which specific aspects of drinking (e.g. lifetime alcohol use vs. alcohol dependence diagnosis) are most genetically correlated with self-reported levels of alcohol consumption. To study particular features of problem drinking, ascertained samples that are enriched for liability to alcohol dependence may provide increased power through larger sample sizes as well as detailed phenotyping. However, it is likely that several factors might moderate the extent to which genetic liability for alcohol consumption in a specific discovery population, such as the older volunteer cohort that comprises the UK Biobank, is associated with problem drinking in an independent sample. One possibility is that genetic overlap might be more pronounced in a similar age group as that comprising the discovery GWAS, possibly due to cohort-specific genetic and environmental influences. Other moderators might include sex, cultural effects, and access to alcohol, as well as family history of alcohol problems.
