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

Anna R Docherty; Donald J Hagler Jr; Matthew S Panizzon; Michael C Neale; Lisa T Eyler; Christine Fennema-Notestine; Carol E Franz; Amy Jak; Michael J Lyons; Daniel A Rinker; Wesley K Thompson; Ming T Tsuang; Anders M Dale; William S Kremen

doi:10.1016/j.neuroimage.2014.11.040

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

Neuroimage. 2015 Feb 1:106:154-60. doi: 10.1016/j.neuroimage.2014.11.040. Epub 2014 Nov 26.

Authors

Affiliations

¹ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23220, USA. Electronic address: [email protected].
² Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
³ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23220, USA.
⁵ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, 92093, CA USA.
⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
⁷ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093, USA.
⁸ Department of Psychology, Boston University, Boston, MA 02215, USA.
⁹ Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁰ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
¹¹ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹² Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
¹³ Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093, USA.

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.

Keywords: Aging; Cognitive ability; Cortical folding; Gyrification; Heritability; Twin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Twin Study

MeSH terms

Cerebral Cortex / pathology*
Cerebral Cortex / physiopathology*
Cognition Disorders / genetics*
Cognition*
Genetic Association Studies
Humans
Male
Middle Aged
Morphogenesis / genetics*
Organ Size / genetics
Phenotype
Twins / genetics*

Abstract

Publication types

MeSH terms

Grants and funding