Major psychiatric disorders including alcohol use disorder are considered multigenic and the smallness of effects of individual genes may be attributed to either complex biological mechanisms or geneenvironment interactions. The latter explanation is highlighted by the relatively fast changes in secular trends and in cohort effects on alcohol use disorder. Interactions of candidate gene variants with birth cohort have been found in the Estonian Children Personality Behaviour and Health Study, a longitudinal investigation from 1998 with a sample highly representative of birth cohorts within a region. Such interactions regarding initiation of alcohol use or alcohol use disorder have been revealed for e.g., 5-HTTLPR, VMAT1, OXR and NRG1, and suggest that rapid alterations in the socioeconomic environment promote changes in the genetic vulnerability to environmental risks factors such as alcohol.