The genetic architecture of the human cerebral cortex

Katrina L Grasby; Nicola J Armstrong; Rachel M Brouwer; Anouk den Braber; Iryna O Fedko; Judith M Ford; Dirk J Heslenfeld; Jouke-Jan Hottenga; Iris E Jansen; Yuri Milaneschi; Gareth E Davies; Dorret I Boomsma; Eco J C de Geus; Jaap Oosterlaan; Brenda W J H Penninx; Tinca J C Polderman; Danielle Posthuma; Dennis van 't Ent; Sarah E Medland; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1126/science.aay6690

The genetic architecture of the human cerebral cortex

Katrina L Grasby, Nicola J Armstrong, Rachel M Brouwer, Anouk den Braber, Iryna O Fedko, Judith M Ford, Dirk J Heslenfeld, Jouke-Jan Hottenga, Iris E Jansen, Yuri Milaneschi, Gareth E Davies, Dorret I Boomsma, Eco J C de Geus, Jaap Oosterlaan, Brenda W J H Penninx, Tinca J C Polderman, Danielle Posthuma, Dennis van 't Ent, Sarah E Medland, Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to Journal › Article › Academic › peer-review

661 Downloads (Pure)

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
Pages (from-to)	1-14
Number of pages	17
Journal	Science
Volume	367
Issue number	6484
DOIs	https://doi.org/10.1126/science.aay6690
Publication status	Published - 20 Mar 2020

Bibliographical note

Funding

Funders	Funder number
National Institute of Biomedical Imaging and Bioengineering	P41EB015922

Cohort Studies

Netherlands Twin Register (NTR)

Access to Document

10.1126/science.aay6690

eaay6690_The genetic architecture of the human cerebral cortexFinal published version, 2.25 MBLicence: Article 25fa Dutch Copyright Act

Persistent URL (handle)

Persistent link

Cite this

Grasby, K. L., Armstrong, N. J., Brouwer, R. M., den Braber, A., Fedko, I. O., Ford, J. M., Heslenfeld, D. J., Hottenga, J.-J., Jansen, I. E., Milaneschi, Y., Davies, G. E., Boomsma, D. I., de Geus, E. J. C., Oosterlaan, J., Penninx, B. W. J. H., Polderman, T. J. C., Posthuma, D., van 't Ent, D., Medland, S. E., & Alzheimer’s Disease Neuroimaging Initiative (2020). The genetic architecture of the human cerebral cortex. Science, 367(6484), 1-14. Article eaay6690. https://doi.org/10.1126/science.aay6690

@article{24e85212901f4109a8bc9246e70bb73d,

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 = "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 Hannah-Ruth Engelbrecht and Susanne Erk and Fan, {Chun Chieh} and Fedko, {Iryna O} and Foley, {Sonya F} and Ford, {Judith M} and Masaki Fukunaga and Garrett, {Melanie E} and Tian Ge and Sudheer Giddaluru and Goldman, {Aaron L} and Green, {Melissa J} and Groenewold, {Nynke A} and Dominik Grotegerd and Gurholt, {Tiril P} and Gutman, {Boris A} and Hansell, {Narelle K} and Harris, {Mathew A} and Harrison, {Marc B} and Haswell, {Courtney C} and Michael Hauser and Stefan Herms and Heslenfeld, {Dirk J} and Ho, {New Fei} and David Hoehn and Per Hoffmann and Laurena Holleran and Martine Hoogman and Jouke-Jan Hottenga and Masashi Ikeda and Deborah Janowitz and Jansen, {Iris E} and Tianye Jia and Christiane Jockwitz and Ryota Kanai and Sherif Karama and Dalia Kasperaviciute and Tobias Kaufmann and Sinead Kelly and Masataka Kikuchi and Marieke Klein and Michael Knapp and Knodt, {Annchen R} and Bernd Kr{\"a}mer and Max Lam and Lancaster, {Thomas M} and Lee, {Phil H} and Lett, {Tristram A} and Lewis, {Lindsay B} and Iscia Lopes-Cendes and Michelle Luciano and Fabio Macciardi and Marquand, {Andre F} and Mathias, {Samuel R} and Melzer, {Tracy R} and Yuri Milaneschi and Nazanin Mirza-Schreiber and Moreira, {Jose C V} and M{\"u}hleisen, {Thomas W} and Bertram M{\"u}ller-Myhsok and Pablo Najt and Soichiro Nakahara and Kwangsik Nho and {Olde Loohuis}, {Loes M} and Orfanos, {Dimitri Papadopoulos} and Pearson, {John F} and Pitcher, {Toni L} and Benno P{\"u}tz and Yann Quid{\'e} and Anjanibhargavi Ragothaman and Rashid, {Faisal M} and Reay, {William R} and Ronny Redlich and Reinbold, {C{\'e}line S} and Jonathan Repple and Genevi{\`e}ve Richard and Riedel, {Brandalyn C} and Risacher, {Shannon L} and Rocha, {Cristiane S} and Mota, {Nina Roth} and Lauren Salminen and Arvin Saremi and Saykin, {Andrew J} and Fenja Schlag and Lianne Schmaal and Schofield, {Peter R} and Rodrigo Secolin and Shapland, {Chin Yang} and Li Shen and Jean Shin and Elena Shumskaya and S{\o}nderby, {Ida E} and Emma Sprooten and Tansey, {Katherine E} and Alexander Teumer and Anbupalam Thalamuthu and Diana Tordesillas-Guti{\'e}rrez and Turner, {Jessica A} and Anne Uhlmann and Vallerga, {Costanza Ludovica} and {van der Meer}, Dennis and {van Donkelaar}, {Marjolein M J} and {van Eijk}, Liza and {van Erp}, {Theo G M} and {van Haren}, {Neeltje E M} and {van Rooij}, Daan and {van Tol}, Marie-Jos{\'e} and Veldink, {Jan H} and Ellen Verhoef and Esther Walton and Mingyuan Wang and Yunpeng Wang and Wardlaw, {Joanna M} and Wei Wen and Westlye, {Lars T} and Whelan, {Christopher D} and Witt, {Stephanie H} and Katharina Wittfeld and Christiane Wolf and Thomas Wolfers and Wu, {Jing Qin} and Yasuda, {Clarissa L} and Dario Zaremba and Zuo Zhang and Zwiers, {Marcel P} and Eric Artiges and Assareh, {Amelia A} and Rosa Ayesa-Arriola and Aysenil Belger and Brandt, {Christine L} and Brown, {Gregory G} and Sven Cichon and Curran, {Joanne E} and Davies, {Gareth E} and Franziska Degenhardt and Dennis, {Michelle F} and Bruno Dietsche and Srdjan Djurovic and Doherty, {Colin P} and Ryan Espiritu and Daniel Garijo and Yolanda Gil and Gowland, {Penny A} and Green, {Robert C} and H{\"a}usler, {Alexander N} and Walter Heindel and Beng-Choon Ho and Hoffmann, {Wolfgang U} and Florian Holsboer and Georg Homuth and Norbert Hosten and Jack, {Clifford R} and MiHyun Jang and Andreas Jansen and Kimbrel, {Nathan A} and Knut Kolsk{\aa}r and Sanne Koops and Axel Krug and Lim, {Kelvin O} and Luykx, {Jurjen J} and Mathalon, {Daniel H} and Mather, {Karen A} and Mattay, {Venkata S} and Sarah Matthews and {Mayoral Van Son}, Jaqueline and McEwen, {Sarah C} and Ingrid Melle and Morris, {Derek W} and Mueller, {Bryon A} and Matthias Nauck and Nordvik, {Jan E} and N{\"o}then, {Markus M} and O'Leary, {Daniel S} and Nils Opel and Martinot, {Marie-Laure Paill{\`e}re} and Pike, {G Bruce} and Adrian Preda and Quinlan, {Erin B} and Rasser, {Paul E} and Varun Ratnakar and Simone Reppermund and Steen, {Vidar M} and Tooney, {Paul A} and Torres, {F{\'a}bio R} and Veltman, {Dick J} and Voyvodic, {James T} and Robert Whelan and Tonya White and Hidenaga Yamamori and Adams, {Hieab H H} and Bis, {Joshua C} and Stephanie Debette and Charles Decarli and Myriam Fornage and Vilmundur Gudnason and Edith Hofer and Ikram, {M Arfan} and Lenore Launer and Longstreth, {W T} and Lopez, {Oscar L} and Bernard Mazoyer and Mosley, {Thomas H} and Roshchupkin, {Gennady V} and Satizabal, {Claudia L} and Reinhold Schmidt and Sudha Seshadri and Qiong Yang and Alvim, {Marina K M} and David Ames and Anderson, {Tim J} and Andreassen, {Ole A} and Alejandro Arias-Vasquez and Bastin, {Mark E} and Baune, {Bernhard T} and Beckham, {Jean C} and John Blangero and Boomsma, {Dorret I} and Henry Brodaty and Brunner, {Han G} and Buckner, {Randy L} and Buitelaar, {Jan K} and Bustillo, {Juan R} and Wiepke Cahn and Cairns, {Murray J} and Vince Calhoun and Carr, {Vaughan J} and Xavier Caseras and Svenja Caspers and Cavalleri, {Gianpiero L} and Fernando Cendes and Aiden Corvin and Benedicto Crespo-Facorro and Dalrymple-Alford, {John C} and Udo Dannlowski and {de Geus}, {Eco J C} and Deary, {Ian J} and Norman Delanty and Chantal Depondt and Sylvane Desrivi{\`e}res and Gary Donohoe and Thomas Espeseth and Guill{\'e}n Fern{\'a}ndez and Fisher, {Simon E} and Herta Flor and Forstner, {Andreas J} and Clyde Francks and Barbara Franke and Glahn, {David C} and Gollub, {Randy L} and Grabe, {Hans J} and Oliver Gruber and H{\aa}berg, {Asta K} and Hariri, {Ahmad R} and Hartman, {Catharina A} and Ryota Hashimoto and Andreas Heinz and Henskens, {Frans A} and Hillegers, {Manon H J} and Hoekstra, {Pieter J} and Holmes, {Avram J} and Hong, {L Elliot} and Hopkins, {William D} and {Hulshoff Pol}, {Hilleke E} and Jernigan, {Terry L} and J{\"o}nsson, {Erik G} and Kahn, {Ren{\'e} S} and Kennedy, {Martin A} and Kircher, {Tilo T J} and Peter Kochunov and Kwok, {John B J} and {Le Hellard}, Stephanie and Loughland, {Carmel M} and Martin, {Nicholas G} and Jean-Luc Martinot and Colm McDonald and McMahon, {Katie L} and Andreas Meyer-Lindenberg and Michie, {Patricia T} and Morey, {Rajendra A} and Bryan Mowry and Lars Nyberg and Jaap Oosterlaan and Ophoff, {Roel A} and Christos Pantelis and Tomas Paus and Zdenka Pausova and Penninx, {Brenda W J H} and Polderman, {Tinca J C} and Danielle Posthuma and Marcella Rietschel and Roffman, {Joshua L} and Rowland, {Laura M} and Sachdev, {Perminder S} and S{\"a}mann, {Philipp G} and Ulrich Schall and Gunter Schumann and Scott, {Rodney J} and Kang Sim and Sisodiya, {Sanjay M} and Smoller, {Jordan W} and Sommer, {Iris E} and {St Pourcain}, Beate and Stein, {Dan J} and Toga, {Arthur W} and Trollor, {Julian N} and {Van der Wee}, {Nic J A} and {van 't Ent}, Dennis and Henry V{\"o}lzke and Henrik Walter and Bernd Weber and Weinberger, {Daniel R} and Wright, {Margaret J} and Juan Zhou and Stein, {Jason L} and Thompson, {Paul M} and Medland, {Sarah E} and {Alzheimer{\textquoteright}s Disease Neuroimaging Initiative}",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2020",

month = mar,

day = "20",

doi = "10.1126/science.aay6690",

language = "English",

volume = "367",

pages = "1--14",

journal = "Science",

issn = "0036-8075",

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

number = "6484",

}

Grasby, KL, Armstrong, NJ, Brouwer, RM , den Braber, A, Fedko, IO, Ford, JM, Heslenfeld, DJ, Hottenga, J-J, Jansen, IE, Milaneschi, Y, Davies, GE, Boomsma, DI , de Geus, EJC , Oosterlaan, J, Penninx, BWJH, Polderman, TJC , Posthuma, D , van 't Ent, D, Medland, SE & Alzheimer’s Disease Neuroimaging Initiative 2020, 'The genetic architecture of the human cerebral cortex', Science, vol. 367, no. 6484, eaay6690, pp. 1-14. https://doi.org/10.1126/science.aay6690

TY - JOUR

T1 - The genetic architecture of the human cerebral cortex

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 - Engelbrecht, Hannah-Ruth

AU - Erk, Susanne

AU - Fan, Chun Chieh

AU - Fedko, Iryna O

AU - Foley, Sonya F

AU - Ford, Judith M

AU - Fukunaga, Masaki

AU - Garrett, Melanie E

AU - Ge, Tian

AU - Giddaluru, Sudheer

AU - Goldman, Aaron L

AU - Green, Melissa J

AU - Groenewold, Nynke A

AU - Grotegerd, Dominik

AU - Gurholt, Tiril P

AU - Gutman, Boris A

AU - Hansell, Narelle K

AU - Harris, Mathew A

AU - Harrison, Marc B

AU - Haswell, Courtney C

AU - Hauser, Michael

AU - Herms, Stefan

AU - Heslenfeld, Dirk J

AU - Ho, New Fei

AU - Hoehn, David

AU - Hoffmann, Per

AU - Holleran, Laurena

AU - Hoogman, Martine

AU - Hottenga, Jouke-Jan

AU - Ikeda, Masashi

AU - Janowitz, Deborah

AU - Jansen, Iris E

AU - Jia, Tianye

AU - Jockwitz, Christiane

AU - Kanai, Ryota

AU - Karama, Sherif

AU - Kasperaviciute, Dalia

AU - Kaufmann, Tobias

AU - Kelly, Sinead

AU - Kikuchi, Masataka

AU - Klein, Marieke

AU - Knapp, Michael

AU - Knodt, Annchen R

AU - Krämer, Bernd

AU - Lam, Max

AU - Lancaster, Thomas M

AU - Lee, Phil H

AU - Lett, Tristram A

AU - Lewis, Lindsay B

AU - Lopes-Cendes, Iscia

AU - Luciano, Michelle

AU - Macciardi, Fabio

AU - Marquand, Andre F

AU - Mathias, Samuel R

AU - Melzer, Tracy R

AU - Milaneschi, Yuri

AU - Mirza-Schreiber, Nazanin

AU - Moreira, Jose C V

AU - Mühleisen, Thomas W

AU - Müller-Myhsok, Bertram

AU - Najt, Pablo

AU - Nakahara, Soichiro

AU - Nho, Kwangsik

AU - Olde Loohuis, Loes M

AU - Orfanos, Dimitri Papadopoulos

AU - Pearson, John F

AU - Pitcher, Toni L

AU - Pütz, Benno

AU - Quidé, Yann

AU - Ragothaman, Anjanibhargavi

AU - Rashid, Faisal M

AU - Reay, William R

AU - Redlich, Ronny

AU - Reinbold, Céline S

AU - Repple, Jonathan

AU - Richard, Geneviève

AU - Riedel, Brandalyn C

AU - Risacher, Shannon L

AU - Rocha, Cristiane S

AU - Mota, Nina Roth

AU - Salminen, Lauren

AU - Saremi, Arvin

AU - Saykin, Andrew J

AU - Schlag, Fenja

AU - Schmaal, Lianne

AU - Schofield, Peter R

AU - Secolin, Rodrigo

AU - Shapland, Chin Yang

AU - Shen, Li

AU - Shin, Jean

AU - Shumskaya, Elena

AU - Sønderby, Ida E

AU - Sprooten, Emma

AU - Tansey, Katherine E

AU - Teumer, Alexander

AU - Thalamuthu, Anbupalam

AU - Tordesillas-Gutiérrez, Diana

AU - Turner, Jessica A

AU - Uhlmann, Anne

AU - Vallerga, Costanza Ludovica

AU - van der Meer, Dennis

AU - van Donkelaar, Marjolein M J

AU - van Eijk, Liza

AU - van Erp, Theo G M

AU - van Haren, Neeltje E M

AU - van Rooij, Daan

AU - van Tol, Marie-José

AU - Veldink, Jan H

AU - Verhoef, Ellen

AU - Walton, Esther

AU - Wang, Mingyuan

AU - Wang, Yunpeng

AU - Wardlaw, Joanna M

AU - Wen, Wei

AU - Westlye, Lars T

AU - Whelan, Christopher D

AU - Witt, Stephanie H

AU - Wittfeld, Katharina

AU - Wolf, Christiane

AU - Wolfers, Thomas

AU - Wu, Jing Qin

AU - Yasuda, Clarissa L

AU - Zaremba, Dario

AU - Zhang, Zuo

AU - Zwiers, Marcel P

AU - Artiges, Eric

AU - Assareh, Amelia A

AU - Ayesa-Arriola, Rosa

AU - Belger, Aysenil

AU - Brandt, Christine L

AU - Brown, Gregory G

AU - Cichon, Sven

AU - Curran, Joanne E

AU - Davies, Gareth E

AU - Degenhardt, Franziska

AU - Dennis, Michelle F

AU - Dietsche, Bruno

AU - Djurovic, Srdjan

AU - Doherty, Colin P

AU - Espiritu, Ryan

AU - Garijo, Daniel

AU - Gil, Yolanda

AU - Gowland, Penny A

AU - Green, Robert C

AU - Häusler, Alexander N

AU - Heindel, Walter

AU - Ho, Beng-Choon

AU - Hoffmann, Wolfgang U

AU - Holsboer, Florian

AU - Homuth, Georg

AU - Hosten, Norbert

AU - Jack, Clifford R

AU - Jang, MiHyun

AU - Jansen, Andreas

AU - Kimbrel, Nathan A

AU - Kolskår, Knut

AU - Koops, Sanne

AU - Krug, Axel

AU - Lim, Kelvin O

AU - Luykx, Jurjen J

AU - Mathalon, Daniel H

AU - Mather, Karen A

AU - Mattay, Venkata S

AU - Matthews, Sarah

AU - Mayoral Van Son, Jaqueline

AU - McEwen, Sarah C

AU - Melle, Ingrid

AU - Morris, Derek W

AU - Mueller, Bryon A

AU - Nauck, Matthias

AU - Nordvik, Jan E

AU - Nöthen, Markus M

AU - O'Leary, Daniel S

AU - Opel, Nils

AU - Martinot, Marie-Laure Paillère

AU - Pike, G Bruce

AU - Preda, Adrian

AU - Quinlan, Erin B

AU - Rasser, Paul E

AU - Ratnakar, Varun

AU - Reppermund, Simone

AU - Steen, Vidar M

AU - Tooney, Paul A

AU - Torres, Fábio R

AU - Veltman, Dick J

AU - Voyvodic, James T

AU - Whelan, Robert

AU - White, Tonya

AU - Yamamori, Hidenaga

AU - Adams, Hieab H H

AU - Bis, Joshua C

AU - Debette, Stephanie

AU - Decarli, Charles

AU - Fornage, Myriam

AU - Gudnason, Vilmundur

AU - Hofer, Edith

AU - Ikram, M Arfan

AU - Launer, Lenore

AU - Longstreth, W T

AU - Lopez, Oscar L

AU - Mazoyer, Bernard

AU - Mosley, Thomas H

AU - Roshchupkin, Gennady V

AU - Satizabal, Claudia L

AU - Schmidt, Reinhold

AU - Seshadri, Sudha

AU - Yang, Qiong

AU - Alvim, Marina K M

AU - Ames, David

AU - Anderson, Tim J

AU - Andreassen, Ole A

AU - Arias-Vasquez, Alejandro

AU - Bastin, Mark E

AU - Baune, Bernhard T

AU - Beckham, Jean C

AU - Blangero, John

AU - Boomsma, Dorret I

AU - Brodaty, Henry

AU - Brunner, Han G

AU - Buckner, Randy L

AU - Buitelaar, Jan K

AU - Bustillo, Juan R

AU - Cahn, Wiepke

AU - Cairns, Murray J

AU - Calhoun, Vince

AU - Carr, Vaughan J

AU - Caseras, Xavier

AU - Caspers, Svenja

AU - Cavalleri, Gianpiero L

AU - Cendes, Fernando

AU - Corvin, Aiden

AU - Crespo-Facorro, Benedicto

AU - Dalrymple-Alford, John C

AU - Dannlowski, Udo

AU - de Geus, Eco J C

AU - Deary, Ian J

AU - Delanty, Norman

AU - Depondt, Chantal

AU - Desrivières, Sylvane

AU - Donohoe, Gary

AU - Espeseth, Thomas

AU - Fernández, Guillén

AU - Fisher, Simon E

AU - Flor, Herta

AU - Forstner, Andreas J

AU - Francks, Clyde

AU - Franke, Barbara

AU - Glahn, David C

AU - Gollub, Randy L

AU - Grabe, Hans J

AU - Gruber, Oliver

AU - Håberg, Asta K

AU - Hariri, Ahmad R

AU - Hartman, Catharina A

AU - Hashimoto, Ryota

AU - Heinz, Andreas

AU - Henskens, Frans A

AU - Hillegers, Manon H J

AU - Hoekstra, Pieter J

AU - Holmes, Avram J

AU - Hong, L Elliot

AU - Hopkins, William D

AU - Hulshoff Pol, Hilleke E

AU - Jernigan, Terry L

AU - Jönsson, Erik G

AU - Kahn, René S

AU - Kennedy, Martin A

AU - Kircher, Tilo T J

AU - Kochunov, Peter

AU - Kwok, John B J

AU - Le Hellard, Stephanie

AU - Loughland, Carmel M

AU - Martin, Nicholas G

AU - Martinot, Jean-Luc

AU - McDonald, Colm

AU - McMahon, Katie L

AU - Meyer-Lindenberg, Andreas

AU - Michie, Patricia T

AU - Morey, Rajendra A

AU - Mowry, Bryan

AU - Nyberg, Lars

AU - Oosterlaan, Jaap

AU - Ophoff, Roel A

AU - Pantelis, Christos

AU - Paus, Tomas

AU - Pausova, Zdenka

AU - Penninx, Brenda W J H

AU - Polderman, Tinca J C

AU - Posthuma, Danielle

AU - Rietschel, Marcella

AU - Roffman, Joshua L

AU - Rowland, Laura M

AU - Sachdev, Perminder S

AU - Sämann, Philipp G

AU - Schall, Ulrich

AU - Schumann, Gunter

AU - Scott, Rodney J

AU - Sim, Kang

AU - Sisodiya, Sanjay M

AU - Smoller, Jordan W

AU - Sommer, Iris E

AU - St Pourcain, Beate

AU - Stein, Dan J

AU - Toga, Arthur W

AU - Trollor, Julian N

AU - Van der Wee, Nic J A

AU - van 't Ent, Dennis

AU - Völzke, Henry

AU - Walter, Henrik

AU - Weber, Bernd

AU - Weinberger, Daniel R

AU - Wright, Margaret J

AU - Zhou, Juan

AU - Stein, Jason L

AU - Thompson, Paul M

AU - Medland, Sarah E

AU - Alzheimer’s Disease Neuroimaging Initiative

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.

UR - http://www.scopus.com/inward/record.url?scp=85082081461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85082081461&partnerID=8YFLogxK

U2 - 10.1126/science.aay6690

DO - 10.1126/science.aay6690

M3 - Article

C2 - 32193296

SN - 0036-8075

VL - 367

SP - 1

EP - 14

JO - Science

JF - Science

IS - 6484

M1 - eaay6690

ER -

The genetic architecture of the human cerebral cortex

Abstract

Bibliographical note

Funding

Cohort Studies

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this