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

Shishikura, M.; Liu, L.; Yu, E.; Zhu, R.; Vilar-Ribo, L.; Cupertino, R. B.; Palmer, A. A.; Sanchez-Roige, S.; Vainik, U.; Morys, F.; Gan-Or, Z.; Misic, B.; Dagher, A.

doi:10.1101/2025.06.05.657840

bioRxiv · 10.1101/2025.06.05.657840

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

Shishikura, M.·Liu, L.·Yu, E.·Zhu, R.·Vilar-Ribo, L.·Cupertino, R. B.·Palmer, A. A.·Sanchez-Roige, S.·Vainik, U.·Morys, F.·Gan-Or, Z.·Misic, B.·Dagher, A.

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Abstract

BackgroundImpulsivity 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. MethodsUsing 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. ResultsWe 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. ConclusionsWe 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.

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Shishikura, M., Liu, L., Yu, E., Zhu, R., Vilar-Ribo, L., Cupertino, R. B., Palmer, A. A., Sanchez-Roige, S., Vainik, U., Morys, F., Gan-Or, Z., Misic, B., Dagher, A.. 2025-06-08. Genomic structural equation modeling of impulsivity and risk-taking traits reveals three latent factors distinctly associated with brain structure and development. https://doi.org/10.1101/2025.06.05.657840

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