To our knowledge, this is the largest GWAS of rigorously-defined AD, comprising 14,904 AD individuals and 37,944 controls. We identified known loci in ADH1B that differed between EU and AA, as well as novel genetic correlations between AD and psychiatric disorders (e.g., schizophrenia), tobacco and cannabis use, and social (e.g., socio-economic deprivation) and behavioral (e.g., educational attainment) outcomes. Analyses also revealed a genetic distinction between GWAS results for alcohol consumption and AD. Although larger sample sizes can be amassed by focusing on quantitative measures of consumption, only the upper tail is relevant to AD (as a medical diagnosis) and even that does not capture other aspects of disordered drinking (e.g., loss of control, withdrawal) directly. Conversely, cases derived from electronic medical records (e.g., ICD codes) result in a high rate of false negatives, while self-screening instruments (e.g. AUDIT scores) are best suited to analyses of disordered drinking when a sufficiently high threshold or score cut-off is applied to focus on severity. Our study has the advantage of greater diagnostic precision via use of semi-structured interviews to diagnose AD systematically in a majority of the constituent studies, and therefore greater interpretability in the context of clinically-important AD.
