Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Authors: Edith Hofer, Gennady V. Roshchupkin, Hieab H.H. Adams, Maria J. Knol, Honghuang Lin, Shuo Li, Habil Zare, Shahzad Ahmad, Nicola J. Armstrong, Claudia L. Satizábal, Manon Bernard, Joshua C. Bis, Nathan A. Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas H. Mosley, Yasaman Saba, Lukas Pirpamer, Stephan Seiler, James T. Becker, Owen Carmichael, Jerome I. Rotter, Bruce M. Psaty, Oscar L. Lopez, Najaf Amin, Sven J. van der Lee, Qiong Yang, Jayandra J. Himali, Pauline Maillard, Alexa Beiser, Charles DeCarli, Sherif Karama, Lindsay B. Lewis, Mathew A. Harris, Mark E. Bastin, Ian J. Deary, A. Veronica Witte, Frauke Beyer, Markus Loeffler, Karen A. Mather, Peter R. Schofield, Anbupalam Thalamuthu, John B. Kwok, Margaret J. Wright, David Ames, Julian N. Trollor, Jiyang Jiang, Henry Brodaty, Wei Wen, Meike W. Vernooij, Albert Hofman, André G. Uitterlinden, Wiro J. Niessen, Katharina Wittfeld, Robin Bülow, Uwe Völker, Zdenka Pausová, G. Bruce Pike, Sophie Maingault, Fabrice Crivello, Christophe Tzourio, Philippe Amouyel, Bernard Mazoyer, Michael C. Neale, Carol E. Franz, Michael J. Lyons, Matthew S. Panizzon, Ole A. Andreassen, Anders M. Dale, Mark W. Logue, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro‐Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Jason L. Stein, Paul M. Thompson, Sarah E. Medland, 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 McMahon, Natalia Shatokhina, Leo Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison E. Ashley‐Koch, Manon Bernard, Rachel M. Brouwer, Elizabeth E.L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, M. Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy‐Duchesne, Anders M. Dale, Shareefa Dalvie, Tânia Kawasaki de Araujo, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O. Fedko, Sonya Foley, Judith M Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc Harrison, Courtney C. Haswell, Michael A. 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 Kasperavičiūtė, Tobias Kaufmann, Sinéad Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R. Knodt, Bernd Krämer, Max Lam, T. Lancaster, Phil Hyu Lee, Tristram A. Lett, Lindsay B. Lewis, Íscia Lopes‐Cendes, Michelle Luciano, Fabìo Macciardi, André F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza‐Schreiber, José Carlos Vasques 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, Anjanibhargavi Ragothaman, Faisal Rashid, Ronny Redlich, Céline S. Reinbold, Jonathan Repple, Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher, Cristiane S. Rocha, Nina Roth Mota, Lauren E. 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 L. Vallerga, Dennis van der Meer, Marjolein M. J. 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, Clarissa Lin Yasuda, Dario Zaremba, Zuo Zhang, Alyssa H. Zhu, Marcel P. Zwiers, Éric Artiges, Amelia A. Assareh, Rosa Ayesa‐Arriola, Ayşenil Belger, Christine L. Brandt, Gregory G. Brown, Sven Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil, Penny Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng‐Choon Ho, Wolfgang Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, MiHyun Jang, Andreas Jansen, 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 McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias Nauck, Jan Egil Nordvik, Markus M. Nöthen, Daniel S. OʼLeary, Nils Opel, Marie‐Laure Paillère Martinot, G. Bruce Pike, Adrian Preda, Erin Burke Quinlan, Varun Ratnakar, Simone Reppermund, Vidar M. Steen, Fábio R. Torres, Dick J. Veltman, James T. Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Marina K. M. Alvim, David Ames, Tim Anderson, Ole A. Andreassen, Alejandro Arias Vásquez, Mark E. Bastin, Bernhard T. Baune, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Juan Bustillo, Wiepke Cahn, Vince D. Calhoun, 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, Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong, William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo Kircher, Peter Kochunov, John B. Kwok, Stéphanie Le Hellard, Nicholas G. Martin, Jean Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer‐Lindenberg, Rajendra A. Morey, Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Tomáš Paus, Zdenka Pausová, Brenda W.J.H. Penninx, Tinca J. C. Polderman, Daniëlle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Perminder S. Sachdev, Philipp G. Sämann, Gunter Schumann, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beaté St Pourcain, Dan J. Stein, Arthur W. Toga, Julian N. Trollor, Nic J.A. 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, Perminder S. Sachdev, William S. Kremen, Joanna M. Wardlaw, Arno Villringer, Cornelia M. van Duijn, Hans J. Grabe, W.T. Longstreth, Myriam Fornage, Tomáš Paus, Stéphanie Debette, M. Arfan Ikram, Helena Schmidt, Reinhold Schmidt, Sudha Seshadri - Nature Communications 2020 cited by 108

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.