Educational attainment polygenic scores, socioeconomic factors, and cortical structure in children and adolescents.

Genome-wide polygenic scores for educational attainment (PGS-EA) and socioeconomic factors, which are correlated with each other, have been consistently associated with academic achievement and general cognitive ability in children and adolescents. Yet, the independent associations of PGS-EA and socioeconomic factors with specific underlying factors at the neural and neurocognitive levels are not well understood. The main goals of this study were to examine the unique contributions of PGS-EA and parental education to cortical structure and neurocognitive skills in children and adolescents, and the associations among PGS-EA, cortical structure, and neurocognitive skills. Participants were typically developing 3- to 21-year-olds (53% male; N = 391). High-resolution, T1-weighted magnetic resonance imaging data were acquired, and cortical thickness (CT) and surface area (SA) were measured. PGS-EA were computed based on the EA3 genome-wide association study of educational attainment. Participants completed executive function, vocabulary, and episodic memory tasks. Higher PGS-EA and parental education were independently and significantly associated with greater total SA and vocabulary. Higher PGS-EA was significantly associated with greater SA in the left medial orbitofrontal gyrus and inferior frontal gyrus, which was associated with higher executive function. Higher parental education was significantly associated with greater SA in the left parahippocampal gyrus after accounting for PGS-EA and total brain volume. These findings suggest that education-linked genetics may influence SA in frontal regions, leading to variability in executive function. Associations of parental education with cortical structure in children and adolescents remained significant after controlling for PGS-EA, a source of genetic confounding.

Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents.

BACKGROUND: Depression has frequently been associated with smaller hippocampal volume. The hippocampus varies in function along its anterior-posterior axis, with the anterior hippocampus more strongly associated with stress and emotion processing. The goals of this study were to examine the associations among parental history of anxiety/depression, polygenic risk scores for depression (PGS-DEP), and anterior and posterior hippocampal volumes in children and adolescents. To examine specificity to PGS-DEP, we examined associations of educational attainment polygenic scores (PGS-EA) with anterior and posterior hippocampal volume. METHODS: Participants were 350 3- to 21-year-olds (46 % female). PGS-DEP and PGS-EA were computed based on recent, large-scale genome-wide association studies. High-resolution, T1-weighted magnetic resonance imaging (MRI) data were acquired, and a semi-automated approach was used to segment the hippocampus into anterior and posterior subregions. RESULTS: Children and adolescents with higher polygenic risk for depression were more likely to have a parent with a history of anxiety/depression. Higher polygenic risk for depression was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA was not associated with anterior or posterior hippocampal volumes. LIMITATIONS: Participants in these analyses were all of European ancestry. CONCLUSIONS: Polygenic risk for depression may lead to smaller anterior but not posterior hippocampal volume in children and adolescents, and there may be specificity of these effects to PGS-DEP rather than PGS-EA. These findings may inform the earlier identification of those in need of support and the design of more effective, personalized treatment strategies. DECLARATIONS OF INTEREST: none. DECLARATIONS OF INTEREST: None.