Dual-systems models of the genetic architecture of impulsive personality traits: Neurogenetic evidence of distinct but related factors

Abstract

BackgroundDual-systems models provide a parsimonious framework for understanding the interplay between cortical and subcortical brain regions relevant to impulsive personality traits (IPTs) and their associations with psychiatric disorders. Despite recent developments in multivariate analysis of genome-wide association studies (GWAS), molecular genetic investigations of these models have not been conducted. MethodsUsing extant IPT GWAS, we conducted confirmatory genomic structural equation models (GenomicSEM) to empirically evaluate dual-systems models of the genetic architecture of IPTs. Genetic correlations between results of multivariate GWAS of dual-systems factors and GWAS of relevant cortical and subcortical neuroimaging phenotypes (regional/structural volume, cortical surface area, cortical thickness) were calculated and compared. ResultsEvaluation of GenomicSEM model fit indices for dual-systems models suggested that these models highlight important sources of shared and unique genetic variance between top-down and bottom-up constructs. Specifically, a dual-systems genomic model consisting of sensation seeking and lack of self-control factors demonstrated distinct but related sources of genetic influences (rg=.60). Genetic correlation analyses provided evidence of differential associations between dual-systems factors and cortical neuroimaging phenotypes (e.g., lack of self-control negatively associated with cortical thickness, sensation seeking positively associated with cortical surface area). However, no significant associations were observed for subcortical phenotypes inconsistent with hypothesized functional localization of dual-systems constructs. ConclusionsDual-systems models of the genetic architecture of IPTs tested here demonstrate evidence of shared and unique genetic influences and associations with relevant neuroimaging phenotypes. These findings emphasize potential advantages in utilizing dual-systems models to study genetic influences for IPTs and transdiagnostic associations with psychiatric disorders.