The dopamine transporter VNTR polymorphism moderates the relationship between acute response to alcohol and future alcohol use disorder symptoms

Alcohol use disorder (AUD) is a genetically influenced disease with peak onset in young adulthood. Identification of factors that predict whether AUD symptoms will diminish or persist after young adulthood is a critical public health need. King and colleagues previously reported that acute response to alcohol predicted future AUD symptom trajectory. Genes associated with brain dopamine signaling, which underlies alcohol's rewarding effects, might influence this finding. This study analyzed whether variation at a variable number tandem repeat polymorphism in DAT1/SLC6A3, the gene encoding the dopamine transporter, moderated the predictive relationships between acute response to alcohol and future AUD symptoms among participants enrolled in the Chicago Social Drinking Project (first two cohorts). Heavy‐drinking young adults (N = 197) completed an alcohol challenge, in which acute response (liking, wanting, stimulation, and sedation) was measured. Alcohol use disorder symptoms were assessed over the following 6 years. DAT1 genotype significantly moderated the interactions between follow‐up time and alcohol liking (P = 0.006) and wanting (P = 0.006) in predicting future AUD symptoms. These predictive effects were strongest among participants who carried the DAT1 9‐repeat allele, previously associated with enhanced striatal dopamine tone relative to the 10‐repeat allele. Exploratory analyses indicated that DAT1 effects on the relationship between alcohol liking and AUD symptoms appeared stronger for females (n = 79) than males (n = 118) (P = 0.0496). These data suggest that heavy‐drinking DAT1 9‐repeat allele carriers who display high alcohol‐induced reward in young adulthood may be predisposed to persistent AUD symptoms and support combining genotypic and phenotypic information to predict future AUD risk. Among heavy drinking young adults followed longitudinally for 6 years, we found that a common genetic polymorphism that putatively regulates striatal dopamine tone influenced relationships between acute response to alcohol and subsequent alcohol use disorder (AUD) symptom trajectories. Greater alcohol liking and wanting more strongly predicted increases in subsequent AUD symptoms among individuals who carried the nine‐repeat allele of a variable number tandem repeat polymorphism in the dopamine transporter (DAT) gene, previously associated with lower striatal DAT availability.