Genomic structural equation modeling of impulsivity and risk-taking traits reveals three latent factors 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 underlying 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 partly differentiated 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 variation in white matter development. We found little evidence that socioeconomic factors modulated associations between polygenic scores and brain structure.

CONCLUSIONS

Using genome-wide association study data of European genetic ancestry samples, we identified three genetically distinct dimensions of impulsivity and risk-taking. These genetic predispositions showed association with brain structure as early as ages 9-10, with limited evidence that these associations varied across socioeconomic context.