The genetic architecture of the human cerebral cortex

Grasby, Katrina;Jahanshad, Neda;Painter, Jodie N.;Colodro-Conde, Lucía;Bralten, Janita;Hibar, Derrek P.;Lind, Penelope A.;Pizzagalli, Fabrizio;Ching, Christopher R. K.;McMahon, Mary Agnes B.;Shatokhina, Natalia;Zsembik, Leo C. P.;Thomopoulos, Sophia I.;Zhu, Alyssa H.;Strike, Lachlan T.;Agartz, Ingrid;Alhusaini, Saud;Almeida, Marcio A. A.;Alnæs, Dag;Amlien, Inge K.;Andersson, Micael;Ard, Tyler;Armstrong, Nicola J.;Ashley-Koch, Allison;Atkins, Joshua R.;Bernard, Manon;Brouwer, Rachel M.;Buimer, Elizabeth E. L.;Bülow, Robin;Bürger, Christian;Cannon, Dara M.;Chakravarty, Mallar;Chen, Qiang;Cheung, Joshua W.;Couvy-Duchesne, Baptiste;Dale, Anders M.;Dalvie, Shareefa;de Araujo, Tânia K.;de Zubicaray, Greig I.;de Zwarte, Sonja M. C.;den Braber, Anouk;Doan, Nhat Trung;Dohm, Katharina;Ehrlich, Stefan;Engelbrecht, Hannah-Ruth;Erk, Susanne;Fan, Chun Chieh;Fedko, Iryna O.;Foley, Sonya F.;Ford, Judith M.;Fukunaga, Masaki;Garrett, Melanie E.;Ge, Tian;Giddaluru, Sudheer;Goldman, Aaron L.;Green, Melissa J.;Groenewold, Nynke A.;Grotegerd, Dominik;Gurholt, Tiril P.;Gutman, Boris A.;Hansell, Narelle K.;Harris, Mathew A.;Harrison, Marc B.;Haswell, Courtney C.;Hauser, Michael;Herms, Stefan;Heslenfeld, Dirk J.;Ho, New Fei;Hoehn, David;Hoffmann, Per;Holleran, Laurena;Hoogman, Martine;Hottenga, Jouke-Jan;Ikeda, Masashi;Janowitz, Deborah;Jansen, Iris E.;Jia, Tianye;Jockwitz, Christiane;Kanai, Ryota;Karama, Sherif;Kasperaviciute, Dalia;Kaufmann, Tobias;Kelly, Sinead;Kikuchi, Masataka;Klein, Marieke;Knapp, Michael;Knodt, Annchen R.;Krämer, Bernd;Lam, Max;Lancaster, Thomas M.;Lee, Phil H.;Lett, Tristram A.;Lewis, Lindsay B.;Lopes-Cendes, Iscia;Luciano, Michelle;Macciardi, Fabio;Marquand, Andre F.;Mathias, Samuel R.;Melzer, Tracy R.;Milaneschi, Yuri;Mirza-Schreiber, Nazanin;Moreira, Jose C. V.;Mühleisen, Thomas W.;Müller-Myhsok, Bertram;Najt, Pablo;Nakahara, Soichiro;Nho, Kwangsik;Olde Loohuis, Loes M.;Orfanos, Dimitri Papadopoulos;Pearson, John F.;Pitcher, Toni L.;Pütz, Benno;Quidé, Yann;Ragothaman, Anjanibhargavi;Rashid, Faisal M.;Reay, William R.;Redlich, Ronny;Reinbold, Céline S.;Repple, Jonathan;Richard, Geneviève;Riedel, Brandalyn C.;Risacher, Shannon L.;Rocha, Cristiane S.;Mota, Nina Roth;Salminen, Lauren;Saremi, Arvin;Saykin, Andrew J.;Schlag, Fenja;Schmaal, Lianne;Schofield, Peter R.;Secolin, Rodrigo;Shapland, Chin Yang;Shen, Li;Shin, Jean;Shumskaya, Elena;Sønderby, Ida E.;Sprooten, Emma;Tansey, Katherine E.;Teumer, Alexander;Thalamuthu, Anbupalam;Tordesillas-Gutiérrez, Diana;Turner, Jessica A.;Uhlmann, Anne;Vallerga, Costanza Ludovica;van der Meer, Dennis;van Donkelaar, Marjolein M. J.;van Eijk, Liza;van Erp, Theo G. M.;van Haren, Neeltje E. M.;van Rooij, Daan;van Tol, Marie-José;Veldink, Jan H.;Verhoef, Ellen;Walton, Esther;Wang, Mingyuan;Wang, Yunpeng;Wardlaw, Joanna M.;Wen, Wei;Westlye, Lars T.;Whelan, Christopher D.;Witt, Stephanie H.;Wittfeld, Katharina;Wolf, Christiane;Wolfers, Thomas;Wu, Jing Qin;Yasuda, Clarissa L.;Zaremba, Dario;Zhang, Zuo;Zwiers, Marcel P.;Artiges, Eric;Assareh, Amelia A.;Ayesa-Arriola, Rosa;Belger, Aysenil;Brandt, Christine L.;Brown, Gregory G.;Cichon, Sven;Curran, Joanne E.;Davies, Gareth E.;Degenhardt, Franziska;Dennis, Michelle F.;Dietsche, Bruno;Djurovic, Srdjan;Doherty, Colin P.;Espiritu, Ryan;Garijo, Daniel;Gil, Yolanda;Gowland, Penny A.;Green, Robert C.;Häusler, Alexander N.;Heindel, Walter;Ho, Beng-Choon;Hoffmann, Wolfgang U.;Holsboer, Florian;Homuth, Georg;Hosten, Norbert;Jack, Clifford R.;Jang, MiHyun;Jansen, Andreas;Kimbrel, Nathan A.;Kolskår, Knut;Koops, Sanne;Krug, Axel;Lim, Kelvin O.;Luykx, Jurjen J.;Mathalon, Daniel H.;Mather, Karen A.;Mattay, Venkata S.;Matthews, Sarah;Mayoral Van Son, Jaqueline;McEwen, Sarah C.;Melle, Ingrid;Morris, Derek W.;Mueller, Bryon A.;Nauck, Matthias;Nordvik, Jan E.;Nöthen, Markus M.;O’Leary, Daniel S.;Opel, Nils;Martinot, Marie-Laure Paillère;Pike, G. Bruce;Preda, Adrian;Quinlan, Erin B.;Rasser, Paul E.;Ratnakar, Varun;Reppermund, Simone;Steen, Vidar M.;Tooney, Paul A.;Torres, Fábio R.;Veltman, Dick J.;Voyvodic, James T.;Whelan, Robert;White, Tonya;Yamamori, Hidenaga;Adams, Hieab H. H.;Bis, Joshua C.;Debette, Stephanie;Decarli, Charles;Fornage, Myriam;Gudnason, Vilmundur;Hofer, Edith;Ikram, M. Arfan;Launer, Lenore;Longstreth, W. T.;Lopez, Oscar L.;Mazoyer, Bernard;Mosley, Thomas H.;Roshchupkin, Gennady V.;Satizabal, Claudia L.;Schmidt, Reinhold;Seshadri, Sudha;Yang, Qiong;Alvim, Marina K. M.;Ames, David;Anderson, Tim J.;Andreassen, Ole A.;Arias-Vasquez, Alejandro;Bastin, Mark E.;Baune, Bernhard T.;Beckham, Jean C.;Blangero, John;Boomsma, Dorret I.;Brodaty, Henry;Brunner, Han G.;Buckner, Randy L.;Buitelaar, Jan K.;Bustillo, Juan R.;Cahn, Wiepke;Cairns, Murray J.;Calhoun, Vince;Carr, Vaughan J.;Caseras, Xavier;Caspers, Svenja;Cavalleri, Gianpiero L.;Cendes, Fernando;Corvin, Aiden;Crespo-Facorro, Benedicto;Dalrymple-Alford, John C.;Dannlowski, Udo;de Geus, Eco J. C.;Deary, Ian J.;Delanty, Norman;Depondt, Chantal;Desrivières, Sylvane;Donohoe, Gary;Espeseth, Thomas;Fernández, Guillén;Fisher, Simon E.;Flor, Herta;Forstner, Andreas J.;Francks, Clyde;Franke, Barbara;Glahn, David C.;Gollub, Randy L.;Grabe, Hans J.;Gruber, Oliver;Håberg, Asta K.;Hariri, Ahmad R.;Hartman, Catharina A.;Hashimoto, Ryota;Heinz, Andreas;Henskens, Frans A.;Hillegers, Manon H. J.;Hoekstra, Pieter J.;Holmes, Avram J.;Hong, L. Elliot;Hopkins, William D.;Hulshoff Pol, Hilleke E.;Jernigan, Terry L.;Jönsson, Erik G.;Kahn, René S.;Kennedy, Martin A.;Kircher, Tilo T. J.;Kochunov, Peter;Kwok, John B. J.;Le Hellard, Stephanie;Loughland, Carmel M.;Martin, Nicholas G.;Martinot, Jean-Luc;McDonald, Colm;McMahon, Katie L.;Meyer-Lindenberg, Andreas;Michie, Patricia T.;Morey, Rajendra A.;Mowry, Bryan;Nyberg, Lars;Oosterlaan, Jaap;Ophoff, Roel A.;Pantelis, Christos;Paus, Tomas;Pausova, Zdenka;Penninx, Brenda W. J. H.;Polderman, Tinca J. C.;Posthuma, Danielle;Rietschel, Marcella;Roffman, Joshua L.;Rowland, Laura M.;Sachdev, Perminder S.;Sämann, Philipp G.;Schall, Ulrich;Schumann, Gunter;Scott, Rodney J.;Sim, Kang;Sisodiya, Sanjay M.;Smoller, Jordan W.;Sommer, Iris E.;St Pourcain, Beate;Stein, Dan J.;Toga, Arthur W.;Trollor, Julian N.;Van der Wee, Nic J. A.;van ’t Ent, Dennis;Völzke, Henry;Walter, Henrik;Weber, Bernd;Weinberger, Daniel R.;Wright, Margaret J.;Zhou, Juan;Stein, Jason L.;Thompson, Paul M.;Medland, Sarah E.

Liza van Eijk

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.

Journal

Science

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N/A

Volume

367

ISBN/ISSN

1095-9203

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Issue

6484

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Publisher

American Association for the Advancement of Science

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DOI

10.1126/science.aay6690