The genetic architecture of the human cerebral cortex

K.L. Grasby*, N. Jahanshad*, J.N. Painter, L. Colodro-Conde, J. Bralten, D.P. Hibar, P.A. Lind, F. Pizzagalli, C.R.K. Ching, M.A.B. McMahon, N. Shatokhina, L.C.P. Zsembik, S.I. Thomopoulos, A.H. Zhu, L.T. Strike, I. Agartz, S. Alhusaini, M.A.A. Almeida, D. Alnaes, I.K. AmlienM. Andersson, T. Ard, N.J. Armstrong, A. Ashley-Koch, J.R. Atkins, M. Bernard, R.M. Brouwer, E.E.L. Buimer, R. Bulow, C. Burger, D.M. Cannon, M. Chakravarty, Q. Chen, J.W. Cheung, B. Couvy-Duchesne, A.M. Dale, S. Dalvie, T.K. de Araujo, G.I. de Zubicaray, S.M.C. de Zwarte, A. den Braber, N.T. Doan, K. Dohm, S. Ehrlich, H.R. Engelbrecht, S. Erk, C.C. Fan, I.O. Fedko, S.F. Foley, J.M. Ford, Dennis van der Meer, Alzheimer's Disease Neuroimaging Initiative, CHARGE Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, EPIGEN Consortium, IMAGEN Consortium, Parkinson's Progression Markers Initiative, SYS Consortium, Han Brunner

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

161 Citations (Web of Science)

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Original languageEnglish
Article number6690
Pages (from-to)1340-+
Number of pages79
JournalScience
Volume367
Issue number6484
DOIs
Publication statusPublished - 20 Mar 2020

Keywords

  • central sulcus
  • common variants
  • cortical sulci
  • expression
  • functional annotation
  • genome-wide association
  • loci
  • metaanalysis
  • observer-independent characterization
  • surface-area
  • CENTRAL SULCUS
  • COMMON VARIANTS
  • CORTICAL SULCI
  • METAANALYSIS
  • SURFACE-AREA
  • LOCI
  • OBSERVER-INDEPENDENT CHARACTERIZATION
  • FUNCTIONAL ANNOTATION
  • EXPRESSION
  • GENOME-WIDE ASSOCIATION

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