Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness

Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e., total surface area, mean cortical thickness) using a genetically informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, where 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recovered loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/ frontal-parietal thickness. Interactome-based analyses revealed significant genetic overlap of global and dorsolateral prefrontal modules, enriched for neurodevelop-mental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.

Automated summary

Human cortical expansion has not occurred uniformly across the brain. By comparing two sets of genome-wide association studies, we assessed the genetic architecture of cortical global expansion and regionalization in 32,488 adults. The genetic factors contributing to total surface area of the cortex expand anterior/frontal regions, while those contributing to thicker cortex increase dorsal/frontal-parietal thickness. The consideration of global measures is important for understanding the genetic variants underlying cortical morphology.