The Genetic Association Between Neocortical Volume and General Cognitive Ability Is Driven by Global Surface Area Rather Than Thickness

Total gray matter volume is associated with general cognitive ability (GCA), an association mediated by genetic factors. It is expectable that total neocortical volume should be similarly associated with GCA. Neocortical volume is the product of thickness and surface area, but global thickness and surface area are unrelated phenotypically and genetically in humans. The nature of the genetic association between GCA and either of these 2 cortical dimensions has not been examined. Humans possess greater cognitive capacity than other species, and surface area increases appear to be the primary driver of the increased size of the human cortex. Thus, we expected neocortical surface area to be more strongly associated with cognition than thickness. Using multivariate genetic analysis in 515 middle-aged twins, we demonstrated that both the phenotypic and genetic associations between neocortical volume and GCA are driven primarily by surface area rather than thickness. Results were generally similar for each of 4 specific cognitive abilities that comprised the GCA measure. Our results suggest that emphasis on neocortical surface area, rather than thickness, could be more fruitful for elucidating neocortical-GCA associations and identifying specific genes underlying those associations.