The genetic architecture of the human cerebral cortex

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group; Katrina L. Grasby; Neda Jahanshad; Jodie N. Painter; Lucía Colodro-conde; Janita Bralten; Derrek P. Hibar; Penelope A. Lind; Fabrizio Pizzagalli; Christopher R. K. Ching; Mary Agnes B. Mcmahon; Natalia Shatokhina; Leo C. P. Zsembik; Sophia I. Thomopoulos; Alyssa H. Zhu; Lachlan T. Strike; Ingrid Agartz; Saud Alhusaini; Marcio A. A. Almeida; Dag Alnæs; Inge K. Amlien; Micael Andersson; Tyler Ard; Nicola J. Armstrong; Allison Ashley-koch; Joshua R. Atkins; Manon Bernard; Rachel M. Brouwer; Elizabeth E. L. Buimer; Robin Bülow; Christian Bürger; Dara M. Cannon; Mallar Chakravarty; Qiang Chen; Joshua W. Cheung; Baptiste Couvy-duchesne; Anders M. Dale; Shareefa Dalvie; Tânia K. De Araujo; Greig I. De Zubicaray; Sonja M. C. De Zwarte; Anouk Den Braber; Nhat Trung Doan; Katharina Dohm; Stefan Ehrlich; Mathew A. Harris; Michelle Luciano; Joanna M. Wardlaw; Colin P. Doherty; Mark E. Bastin; Ian J. Deary

doi:10.1126/science.aay6690

The genetic architecture of the human cerebral cortex

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R. K. Ching, Mary Agnes B. Mcmahon, Natalia Shatokhina, Leo C. P. Zsembik, Sophia I. Thomopoulos, Alyssa H. Zhu, Lachlan T. Strike, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag AlnæsInge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison Ashley-koch, Joshua R. Atkins, Manon Bernard, Rachel M. Brouwer, Elizabeth E. L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-duchesne, Anders M. Dale, Shareefa Dalvie, Tânia K. De Araujo, Greig I. De Zubicaray, Sonja M. C. De Zwarte, Anouk Den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Mathew A. Harris, Michelle Luciano, Joanna M. Wardlaw, Colin P. Doherty, Mark E. Bastin, Ian J. Deary

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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	14
Journal	Science
Volume	367
Issue number	6484
DOIs	https://doi.org/10.1126/science.aay6690
Publication status	Published - 20 Mar 2020

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GrasbyEtalS2020TheGeneticArchitecture
This is the accepted version of the following article: The genetic architecture of the human cerebral cortex 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., Alnæs, D., Amlien, I. K. & 340 others, , 20 Mar 2020, In : Science. 367, 6484, eaay6690., which has been published in final form at https://science.sciencemag.org/content/367/6484/eaay6690.
Accepted author manuscript, 3.29 MB

The Disconnected Mind Phase 3
Cox, S. & Deary, I.
UK-based charities
1/04/16 → 31/03/23
Project: Research
Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III
Wardlaw, J., Bastin, M. & Deary, I.
MRC
1/05/15 → 30/04/19
Project: Research
RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Porteous, D.
1/09/13 → 31/08/19
Project: Research

Mark Bastin
- Deanery of Clinical Sciences - Personal Chair of Brain Imaging
- Centre for Clinical Brain Sciences
- Euan MacDonald Centre for Motor Neuron Disease Research
- Edinburgh Neuroscience
- Edinburgh Imaging
Person: Academic: Research Active

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Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, 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., ... Deary, I. J. (2020). The genetic architecture of the human cerebral cortex. Science, 367(6484), Article eaay6690. https://doi.org/10.1126/science.aay6690

@article{2ad2fee5a1cb432b81a0283158c2db79,

title = "The genetic architecture of the human cerebral cortex",

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.",

author = "{Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group} and Grasby, {Katrina L.} and Neda Jahanshad and Painter, {Jodie N.} and Luc{\'i}a Colodro-conde and Janita Bralten and Hibar, {Derrek P.} and Lind, {Penelope A.} and Fabrizio Pizzagalli and Ching, {Christopher R. K.} and Mcmahon, {Mary Agnes B.} and Natalia Shatokhina and Zsembik, {Leo C. P.} and Thomopoulos, {Sophia I.} and Zhu, {Alyssa H.} and Strike, {Lachlan T.} and Ingrid Agartz and Saud Alhusaini and Almeida, {Marcio A. A.} and Dag Aln{\ae}s and Amlien, {Inge K.} and Micael Andersson and Tyler Ard and Armstrong, {Nicola J.} and Allison Ashley-koch and Atkins, {Joshua R.} and Manon Bernard and Brouwer, {Rachel M.} and Buimer, {Elizabeth E. L.} and Robin B{\"u}low and Christian B{\"u}rger and Cannon, {Dara M.} and Mallar Chakravarty and Qiang Chen and Cheung, {Joshua W.} and Baptiste Couvy-duchesne and Dale, {Anders M.} and Shareefa Dalvie and {De Araujo}, {T{\^a}nia K.} and {De Zubicaray}, {Greig I.} and {De Zwarte}, {Sonja M. C.} and {Den Braber}, Anouk and Doan, {Nhat Trung} and Katharina Dohm and Stefan Ehrlich and Harris, {Mathew A.} and Michelle Luciano and Wardlaw, {Joanna M.} and Doherty, {Colin P.} and Bastin, {Mark E.} and Deary, {Ian J.}",

year = "2020",

month = mar,

day = "20",

doi = "10.1126/science.aay6690",

language = "English",

volume = "367",

journal = "Science",

issn = "0036-8075",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

number = "6484",

}

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, 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, Alnæs, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bülow, R, Bürger, 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, Harris, MA, Luciano, M , Wardlaw, JM, Doherty, CP, Bastin, ME & Deary, IJ 2020, 'The genetic architecture of the human cerebral cortex', Science, vol. 367, no. 6484, eaay6690. https://doi.org/10.1126/science.aay6690

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

AU - Grasby, Katrina L.

AU - Jahanshad, Neda

AU - Painter, Jodie N.

AU - Colodro-conde, Lucía

AU - Bralten, Janita

AU - Hibar, Derrek P.

AU - Lind, Penelope A.

AU - Pizzagalli, Fabrizio

AU - Ching, Christopher R. K.

AU - Mcmahon, Mary Agnes B.

AU - Shatokhina, Natalia

AU - Zsembik, Leo C. P.

AU - Thomopoulos, Sophia I.

AU - Zhu, Alyssa H.

AU - Strike, Lachlan T.

AU - Agartz, Ingrid

AU - Alhusaini, Saud

AU - Almeida, Marcio A. A.

AU - Alnæs, Dag

AU - Amlien, Inge K.

AU - Andersson, Micael

AU - Ard, Tyler

AU - Armstrong, Nicola J.

AU - Ashley-koch, Allison

AU - Atkins, Joshua R.

AU - Bernard, Manon

AU - Brouwer, Rachel M.

AU - Buimer, Elizabeth E. L.

AU - Bülow, Robin

AU - Bürger, Christian

AU - Cannon, Dara M.

AU - Chakravarty, Mallar

AU - Chen, Qiang

AU - Cheung, Joshua W.

AU - Couvy-duchesne, Baptiste

AU - Dale, Anders M.

AU - Dalvie, Shareefa

AU - De Araujo, Tânia K.

AU - De Zubicaray, Greig I.

AU - De Zwarte, Sonja M. C.

AU - Den Braber, Anouk

AU - Doan, Nhat Trung

AU - Dohm, Katharina

AU - Ehrlich, Stefan

AU - Harris, Mathew A.

AU - Luciano, Michelle

AU - Wardlaw, Joanna M.

AU - Doherty, Colin P.

AU - Bastin, Mark E.

AU - Deary, Ian J.

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.

U2 - 10.1126/science.aay6690

DO - 10.1126/science.aay6690

M3 - Article

SN - 0036-8075

VL - 367

JO - Science

JF - Science

IS - 6484

M1 - eaay6690

ER -

The genetic architecture of the human cerebral cortex

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The Disconnected Mind Phase 3

Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III

RA2662 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.

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Mark Bastin

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