Genomic structural equation modeling of impulsivity and risk-taking traits reveals three latent factors distinctly associated with brain structure and development

Background Impulsivity is a multifaceted transdiagnostic trait that emerges in childhood. Research has identified genetic loci and brain systems associated with different facets of impulsivity and risk-taking. However, how these genetic underpinnings overlap across different facets, and how they are associated with brain development during childhood remain unknown. Methods Using genomic structural equation modeling on 17 impulsivity and risk-taking traits, we identified latent factors capturing overlapping genetic architecture. We then calculated polygenic scores for these factors using Adolescent Brain Cognitive Development Study data (N = 4,142) and examined their associations with brain structure, development, and behavior in children aged 9-14 years. Finally, we tested whether socioeconomic status modulated the associations between latent polygenic scores and brain structures. Results We identified three distinct genetic latent factors, which we label lack of self-control, reward drive, and sensation seeking. In children, polygenic scores for the three factors showed associations with distinct brain patterns: lack of self-control associated with reduced prefrontal cortical thickness, reward drive with increased subcortical cellular density, and sensation seeking with increased cortical surface area and white matter integrity. Longitudinally, lack of self-control predicted slower white matter development. The association between polygenetic score for lack of self-control and white matter mean diffusivity was modulated by socioeconomic status. Conclusions We identified three genetically distinct dimensions of impulsivity and risk-taking with separable neurodevelopmental origins. These genetic predispositions manifested as distinct brain patterns as early as ages 9-10. Environmental experience modulated some of the genetic effects on brain development.