Impulsivity facets and substance use involvement: Insights from genomic structural equation modeling

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 (rG=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 (rG=.0.30-0.50) and SUD (rG=0.38-0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 versus rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.31 versus rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=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.