Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

Associations between stage-based phenotypes and alcohol transitions. (a) Associations between internalizing and externalizing and hazards of alcohol transitions. Asterisks reflect estimates that survived FDR correction for all 20 tests for internalizing phenotypes, and separately, all 16 tests for externalizing phenotypes. Note three violations of the proportional hazards assumption for which time interactions were incorporated to resolve the violations: ADHD hyperactive symptoms in models of ‘First Drink’ and ‘First Drink to First Intoxication’ and ODD symptoms in the model of ‘First Drink to First Diagnosis.’ For simplicity, those interactions are not depicted here. All predictors were entered into the models simultaneously, alongside covariates. (b) Associations between executive function and hazards of alcohol transitions. ToL, Tower of London Test; VST, Visual Span Test. Note that for the ToL, higher scores reflect worse executive functioning, whereas the opposite is true for the VST. Hazard ratios for ToL measures are hazards associated with a doubling of the ToL measures, which were log2 transformed (Supplemental Methods). Each EF predictor was entered into analyses separately, given varying sample sizes and correlations among EF phenotypes. For both figures, point estimates reflect hazard ratios, and error bars represent 95% confidence intervals.

Associations between alcohol milestones and stage-based symptom onsets. Associations between alcohol milestones and hazards of stage-based symptom onsets. Point estimates reflect hazard ratios, and error bars represent 95% confidence intervals. Asterisks reflect estimates that survived FDR correction for all (24) tests. MDE, Major Depressive Episode; Panic, Panic Disorder Symptoms; Conduct, Conduct Disorder Symptoms; Oppositional, Oppositional Defiant Disorder Symptoms.

Associations between stage-based polygenic scores and alcohol transitions. Associations between stage-based PGS and hazards of alcohol transitions. EUR, PCA-selected European ancestry; AFR, PCA-selected African ancestry. Point estimates reflect hazard ratios, and error bars represent 95% confidence intervals. AFR ancestry PGS associations are depicted with dotted lines. Alcohol PGS are included for comparison at the bottom of each plot.

Associations between alcohol polygenic scores and stage-based outcomes. Associations between alcohol PGS and hazards of stage-based outcomes. Point estimates reflect hazard ratios, and error bars represent 95% confidence intervals. Solid lines represent PGS in EUR ancestry, and dashed lines represent PGS in AFR ancestry Asterisks reflect estimates that survived FDR correction for all 12 tests (2 alcohol PGS × 6 outcomes) in EUR ancestry. Note that, among individuals of AFR ancestry, models predicting panic symptoms, social anxiety symptoms, and oppositional defiant symptoms did not converge, so estimates may be unreliable.