Fig. 1.

Candidate genes for alcohol dependence characterized into stages of the addiction cycle. This schematic shows the three stages of the addiction cycle: (1): binge-intoxication (blue), (2): withdrawal-negative affect (red) and (3): preoccupation-anticipation (green); also shown are behavioral domains linked to each stage of the cycle: incentive salience, negative emotionality, and executive function, respectively. Candidate functional genes identified by non-GWAS approaches are shown in ovals and colored coded according to the relevant addiction stage the gene is hypothesized to function. GWAS candidates are shown in rectangles color coded according to the relevant addiction stage the gene is hypothesized to function. The general biological function of each gene in the figure is highlighted in black. Non-GWAS functional gene relationships are indicated by overlapping ovals. Hypothesized functional relationships between non-GWAS genes and GWAS candidates are indicated by overlapping ovals and rectangles. GWAS candidates in each stage are grouped according to potential biological functional similarities where possible. Finally, one example of pleiotropy is shown in the preoccupation-anticipation stage. BDNF-COMT functional variants have pleiotropic effects in both the preoccupation-anticipation stage and the withdrawal-negative affect stage. This pleiotropic relationship is shown by dual-color shading of the BDNF-COMT ovals reflecting both addiction stages.