Polygenic Scores for Neuropsychiatric Traits and White Matter Microstructure in the Pediatric Population

Genome-wide association studies have identified numerous genetic variants that predispose to neuropsychiatric traits. Identification of mechanisms in the brain that underlie these associations is essential for understanding manifestations of genetic predisposition within the general population. Here, we investigated the association between polygenic scores (PGSs) for seven neuropsychiatric traits and white matter microstructure of the brain on diffusion tensor imaging in the pediatric population.

Participants from the Generation R Study who had genotype and diffusion tensor imaging data available (n = 1138, mean age = 10.2 years, range = 8.7-12.0) were included. PGSs were calculated for five psychiatric disorders (attention-deficit/hyperactivity disorder, bipolar disorder, autism, major depressive disorder, and schizophrenia) and two cognitive traits (intelligence and educational attainment) and were tested for associations with global and tract-specific fractional anisotropy (FA) and mean diffusivity.

Significant positive associations with global FA were observed for the PGSs of intelligence (β = .109, SE = .029, p < .001, ΔR² = .012) and educational attainment (β = .118, SE = .029, p < .001, ΔR² = .014). No significant associations were observed with FA for the PGSs of psychiatric disorders. Tract-specific analysis showed that the PGSs for intelligence and educational attainment were associated with FA of several association and projection fibers of the brain.

Our results show that genetic predisposition for cognition-related traits, but not for psychiatric disorders, is associated with microstructural diffusion measures of white matter tracts at an early age. These results suggest a shared genetic etiology among structural connectivity, intelligence, and educational achievement.