UC San Diego

BACKGROUND: Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear. METHODS: We used genomic structural equation modeling and genome-wide association studies (N = 79,729-903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits. RESULTS: We found that the SU and SUD factors were strongly genetically inter-correlated (r_G=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (r_G=.0.30-0.50) and SUD (r_G=0.38-0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (r_G=0.27 versus r_G=0.10); delay discounting was more strongly genetically correlated with the SUD factor (r_G=0.31 versus r_G=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (r_G=0.10). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation was independently genetically associated with both the SU (β=0.42) and SUD factors (β=0.21); sensation seeking and positive urgency were independently genetically associated with the SU factor (β=0.48, β=0.33, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.33, β=0.36, respectively). CONCLUSIONS: Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.