Chun Chieh Fan

There remains little consensus about the relationship between sex and brain structure, particularly in early adolescence. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest—many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt‐gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9–11 years old ( N = 7195). Then, a statistical model‐building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. Additional sensitivity analyses found that male versus female differences in gyrification and white matter were largely accounted for by total brain volume, rather than sex per se. The model with sex, but not gender diversity, was the best‐fitting model in 60.1% of gray matter regions and 61.9% of white matter regions after adjusting for brain volume. The proportion of variance accounted for by sex was negligible to small in all cases. While models including felt‐gender explained a greater amount of variance in a few regions, the felt‐gender score alone was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9–11 years old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity.

To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca’s area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.