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. Amlien; M. 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

doi:10.1126/science.aay6690

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 journal › Article › Academic › peer-review

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 language	English
Article number	eaay6690
Number of pages	79
Journal	Science
Volume	367
Issue number	6484
DOIs	https://doi.org/10.1126/science.aay6690
Publication status	Published - 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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Cite this

Grasby, K. L., Jahanshad, N., Painter, J. N., Colodro-Conde, L., Bralten, J., Hibar, D. P., Lind, P. A., Pizzagalli, F., Ching, C. R. K., McMahon, M. A. B., Shatokhina, N., Zsembik, L. C. P., Thomopoulos, S. I., Zhu, A. H., Strike, L. T., Agartz, I., Alhusaini, S., Almeida, M. A. A., Alnaes, D., ... Brunner, H. (2020). The genetic architecture of the human cerebral cortex. Science, 367(6484), Article eaay6690. https://doi.org/10.1126/science.aay6690

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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.",

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",

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

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doi = "10.1126/science.aay6690",

language = "English",

volume = "367",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6484",

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Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Doan, NT, Dohm, K, Ehrlich, S, Engelbrecht, HR, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, van der Meer, D, 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 & Brunner, H 2020, 'The genetic architecture of the human cerebral cortex', Science, vol. 367, no. 6484, eaay6690. https://doi.org/10.1126/science.aay6690

TY - JOUR

T1 - The genetic architecture of the human cerebral cortex

AU - Grasby, K.L.

AU - Jahanshad, N.

AU - Painter, J.N.

AU - Colodro-Conde, L.

AU - Bralten, J.

AU - Hibar, D.P.

AU - Lind, P.A.

AU - Pizzagalli, F.

AU - Ching, C.R.K.

AU - McMahon, M.A.B.

AU - Shatokhina, N.

AU - Zsembik, L.C.P.

AU - Thomopoulos, S.I.

AU - Zhu, A.H.

AU - Strike, L.T.

AU - Agartz, I.

AU - Alhusaini, S.

AU - Almeida, M.A.A.

AU - Alnaes, D.

AU - Amlien, I.K.

AU - Andersson, M.

AU - Ard, T.

AU - Armstrong, N.J.

AU - Ashley-Koch, A.

AU - Atkins, J.R.

AU - Bernard, M.

AU - Brouwer, R.M.

AU - Buimer, E.E.L.

AU - Bulow, R.

AU - Burger, C.

AU - Cannon, D.M.

AU - Chakravarty, M.

AU - Chen, Q.

AU - Cheung, J.W.

AU - Couvy-Duchesne, B.

AU - Dale, A.M.

AU - Dalvie, S.

AU - de Araujo, T.K.

AU - de Zubicaray, G.I.

AU - de Zwarte, S.M.C.

AU - den Braber, A.

AU - Doan, N.T.

AU - Dohm, K.

AU - Ehrlich, S.

AU - Engelbrecht, H.R.

AU - Erk, S.

AU - Fan, C.C.

AU - Fedko, I.O.

AU - Foley, S.F.

AU - Ford, J.M.

AU - van der Meer, Dennis

AU - Alzheimer's Disease Neuroimaging Initiative

AU - CHARGE Consortium

AU - Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group

AU - EPIGEN Consortium

AU - IMAGEN Consortium

AU - Parkinson's Progression Markers Initiative

AU - SYS Consortium

AU - Brunner, Han

PY - 2020/3/20

Y1 - 2020/3/20

N2 - 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.

AB - 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.

KW - central sulcus

KW - common variants

KW - cortical sulci

KW - expression

KW - functional annotation

KW - genome-wide association

KW - loci

KW - metaanalysis

KW - observer-independent characterization

KW - surface-area

KW - CENTRAL SULCUS

KW - COMMON VARIANTS

KW - CORTICAL SULCI

KW - METAANALYSIS

KW - SURFACE-AREA

KW - LOCI

KW - OBSERVER-INDEPENDENT CHARACTERIZATION

KW - FUNCTIONAL ANNOTATION

KW - EXPRESSION

KW - GENOME-WIDE ASSOCIATION

U2 - 10.1126/science.aay6690

DO - 10.1126/science.aay6690

M3 - Article

C2 - 32193296

SN - 0036-8075

VL - 367

JO - Science

JF - Science

IS - 6484

M1 - eaay6690

ER -