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The genetic architecture of the human cerebral cortex

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

Posted 03 Sep 2018
bioRxiv DOI: 10.1101/399402

The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P ≤ 5 x 10-8); 199 survived multiple testing correction (P ≤ 8.3 x 10-10; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression and ADHD. NOTE: K.L.G. and N.J. contributed to this work as co-first authors for this preprint. J.N.P., L.C.-C., J.B., D.P.H., P.A.L., F.P. contributed to this work as co-second authors for this preprint. J.L.S., P.M.T., S.E.M. contributed to this work as co-last authors for this preprint.

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