The expansion of the human cerebral cortex relative to other non-human primates is thought to underlie our uniquely human cognitive capabilities. Deviations in the morphology of specific cortical regions are correlated with various cognitive abilities and psychiatric disorders. Results from family studies have indicated a genetic relationship between some differences in the cortex certain psychiatric disorders. Using the results from GWAS meta-analyses of the thickness and surface area of cortical regions derived from structural magnetic resonance imaging (MRI) scans from ~35,000 individuals, we applied LDscore regression to estimate the heritability of and the genetic correlations among cortical regions. Using partitioned heritability, we assessed differential enrichment patterns between total surface area and average thickness. Genetic correlations between cortical regions and cognitive ability and psychiatric disorders were estimated using summary statistics from large published GWAS.
Results from the meta-analyses demonstrate that common variation substantially influences the architecture of the human cortex (h2SNP = 0.33 for total surface area and h2SNP = 0.25 for average thickness). A modest negative genetic correlation (rG = -.32, p = 3.9 x 10-11) supports findings from twin studies that genetic influences on thickness and surface area are largely independent. We identified significant enrichment for loci influencing total surface area in regulatory regions of the developing fetal brain, specifically in the progenitor associated germinal zone. For average thickness, heritability was significantly enriched in adult brain. This provides support for the radial unit hypothesis in humans and implies that common genetic variation impacts progenitor associated gene regulation during fetal development to influence post-natal surface area.
Examining the 34 specific regions of the cortex, heritability was greater for surface area (h2SNP 0.09–0.31) than for thickness (h2SNP 0.01–0.16). Consistent with findings from twin studies, genetic correlations within a region were typically negative, with the exception of structures in the occipital lobe. Between the surface area regions, genetic correlations of adjacent regions were typically positive and particularly strong among the structures in the occipital lobe. There were fewer significant genetic correlations between thickness measures of cortical regions and most were strongly negative. These bivariate findings will be compared and contrasted with results from clustering and factoring of areal heritability.
In addition, significant positive genetic correlations were observed between total surface area and IQ, educational attainment, and Parkinson’s disease, while negative genetic correlations were observed with neuroticism, depression, attention deficit hyperactivity disorder, and insomnia. In contrast, no significant genetic correlations were observed between average thickness and any disorders. This contrasts with the findings of phenotypic correlations between cortical thickness and various psychiatric disorders and psychological traits. Genetic correlations of specific regions were observed for IQ, educational attainment, neuroticism, depression, epilepsy, and schizophrenia and results will be discussed.
Neuropsychology (e.g. Dyslexia, Handedness, Language)
