title: Does degree of gyrification underlie the phenotypic and genetic associations between cortical surface area and cognitive ability?
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.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23220, USA. Electronic address: ardocherty@vcu.edu.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Docherty
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: 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.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23220, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: 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.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: 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.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: 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.
authors.forename: Amy
authors.initials: A
authors.lastname: Jak
authors.affiliation: Department of Psychology, Boston University, Boston, MA 02215, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: 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.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Rinker
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: 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.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: 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.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: 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.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009024:Morphogenesis / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D010641:Phenotype; D014427:Twins / Q000235:genetics*
keywords: Aging; Cognitive ability; Cortical folding; Gyrification; Heritability; Twin