Alcohol use disorder (AUD) and related traits provide one of the very few examples of the survival into the current ‘Big Data’ era of large-effect loci initially identified by candidate gene studies8. We discuss these loci — the alcohol metabolism genes alcohol dehydrogenase 1B (class I), beta polypeptide (ADH1B) and aldehyde dehydrogenase 2 family member (ALDH2) — in the predisposition to alcohol use, abuse, and dependence, in the section “From large-effect risk loci to disease biology”. However, these large-effect alleles explain very little of the overall phenotypic variance, which is accounted for by the contribution of thousands of alleles with small effects (i.e., polygenicity). Large-scale GWAS are beginning to reveal the polygenic architecture of several alcohol-related traits, while identifying genetic differences between them that were not appreciated in the days of small-scale studies. Many traits have been considered in GWAS of alcohol use (Box 1). Alcohol use disorder (AUD by the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5); alcohol dependence (AD) by DSM-IV and earlier) seeks to capture physiological dependence, which is an inability to discontinue use
