Genetic Predisposition to Sensation Seeking Predicts Early Alcohol and Substance Use in Teens

Among 4,808 adolescents in the ABCD Study, sensation-seeking polygenic scores significantly predicted any substance use initiation (OR > 1.10) and alcohol use initiation by age 15. Positive urgency PGS predicted nicotine initiation (OR > 1.06). No polygenic scores were significantly associated with cannabis use initiation specifically. Measured impulsivity accounted for only 5-9% of PGS-substance use associations.

Analysis of 4,808 European-ancestry participants in the ABCD Study. Polygenic scores for five UPPS-P impulsivity domains tested against substance use initiation by age 15. Mediation models assessed whether measured child impulsivity (ages 9-11) explained PGS-substance use links.

Understanding which genetic dispositions toward impulsivity drive early substance use helps target prevention efforts. The finding that sensation seeking, not urgency or lack of premeditation, is the key genetic pathway suggests prevention should focus on providing alternative high-stimulation activities.

Not all impulsivity is created equal. This study shows that the genetic architecture of sensation seeking specifically, rather than general impulsiveness, drives early substance experimentation. The lack of a genetic impulsivity link for cannabis specifically suggests other factors may be more important for cannabis initiation.

Limited to European-ancestry participants. PGS capture only a fraction of genetic risk. Self-reported substance use initiation. Short follow-up (to age 15). Cannot rule out gene-environment correlation.