Two studies have previously evaluated the causal effect of AC on depression using MR. Almeida et al., investigated the impact of ADH1B rs1229984 in a sample of 3873 men and did not find evidence of a causal influence on depression (Almeida et al., 2014). In another study, the causal influence of two alcohol dehydrogenase (ADH) genes, ADH1B (rs1229984) and ADH1C (rs698) on depression was assessed in a sample of 68 486 participants from the general population and reported a lack of evidence for a causal influence on depression (Wium-Andersen et al., 2015). However, these studies did not investigate the causal influence of MD on AC or on AD risk. Furthermore, explorations of the causal nature were based on ADH candidate genetic variants only, which does not model the polygenic nature of these disorders.
