What can GWAS tell us about the genetic architecture of the human cortex: Results from the ENIGMA consortium GWAS meta-analyses of cortical thickness and surface area

While cortical thickness and surface area are both strongly heritable, the two processes are genetically independent and there is little known about the loci influencing these morphological characteristics. We will present... [ view full abstract ]

While cortical thickness and surface area are both strongly heritable, the two processes are genetically independent and there is little known about the loci influencing these morphological characteristics. We will present results from GWAS meta-analyses of the thickness and surface area of cortical regions of interest derived from magnetic resonance imaging (MRI) scans from a meta-analysis of ~35,000 individuals.

Across cohorts, structural T1-weighted MRI brain scans were analysed locally using harmonized analysis and quality-control protocols. Cortical parcellations were performed with freely available and validated segmentation software.

Cortical measurements were averaged across the hemispheres resulting in the average thickness and surface area of 34 gray matter regions. We also analyzed two summary measures, average cortical thickness across regions and total surface area. Corrections for the summary measures were included in the regional measures to account for the omnibus effects of brain size.

 Results from the meta-analyses demonstrate that common variation substantially influences the architecture of the human cortex and supports the findings from twin studies that genetic influences on thickness and surface area are largely orthogonal. Across phenotypes we find over 270 regions P=5e-08 with over 95 surviving correction for multiple testing. Unlike our previous work on the subcortical structures, we find the effects of genetic variants often to impact a number of neighboring regions, reflecting the influence of areal patterning factors during human cortical development. Key findings and the distributions of effect sizes will be discussed.