LAUSR

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. Description Genes control cortical surface area Humans exhibit heritable variation in brain structure and function. To identify how gene variants affect the cerebral cortex, Makowski et al. performed genome-wide association studies in almost 40,000 adults and 9000 children. They identified more than 400 loci associated with brain surface area and cortical thickness that could be observed through magnetic resonance imaging analyses. Examining biological pathways linking gene variants to phenotypes identified region-specific enrichments of neurodevelopmental functions, some of which were associated with psychiatric disorders. Partitioning genes with heritable variants relative to evolutionary conservation helped to identify a hierarchy of brain development. This analysis identified a human-specific gene-phenotype association related to speech and informs upon what genes can be studied in various model organisms. —LMZ Genetically informed brain atlases reveal genomic loci affecting neurodevelopmental patterning.