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Does degree of gyrification underlie the phenotypic and genetic associations between cortical surface area and cognitive ability?

  • Author(s): Docherty, Anna R
  • Hagler, Donald J
  • Panizzon, Matthew S
  • Neale, Michael C
  • Eyler, Lisa T
  • Fennema-Notestine, Christine
  • Franz, Carol E
  • Jak, Amy
  • Lyons, Michael J
  • Rinker, Daniel A
  • Thompson, Wesley K
  • Tsuang, Ming T
  • Dale, Anders M
  • Kremen, William S
  • et al.
Abstract

The phenotypic and genetic relationship between global cortical size and general cognitive ability (GCA) appears to be driven by surface area (SA) and not cortical thickness (CT). Gyrification (cortical folding) is an important property of the cortex that helps to increase SA within a finite space, and may also improve connectivity by reducing distance between regions. Hence, gyrification may be what underlies the SA-GCA relationship. In previous phenotypic studies, a 3-dimensional gyrification index (3DGI) has been positively associated with cognitive ability and negatively associated with mild cognitive impairment, Alzheimer's disease, and psychiatric disorders affecting cognition. However, the differential genetic associations of 3DGI and SA with GCA are still unclear. We examined the heritability of 3DGI, and the phenotypic, genetic, and environmental associations of 3DGI with SA and GCA in a large sample of adult male twins (N = 512). Nearly 85% of the variance in 3DGI was due to genes, and 3DGI had a strong phenotypic and genetic association with SA. Both 3DGI and total SA had positive phenotypic correlations with GCA. However, the SA-GCA correlation remained significant after controlling for 3DGI, but not the other way around. There was also significant genetic covariance between SA and GCA, but not between 3DGI and GCA. Thus, despite the phenotypic and genetic associations between 3DGI and SA, our results do not support the hypothesis that gyrification underlies the association between SA and GCA.

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