The genetic architecture of the human cerebral cortex

作者：Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro‐Conde, Janita Bralten, Derrek Paul Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R. K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo Charles Peek Zsembik, Sophia I. Thomopoulos, Alyssa H. Zhu, Lachlan T. Strike, Ingrid Agartz, Saud Alhusaini, Marcio Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler D. Ard, Nicola Jane Armstrong, Allison E. Ashley‐Koch, Joshua Ronald Atkins, Manon Bernard, Rachel M. Brouwer, Elizabeth E.L. Buimer, Robin Bülow, Christian P. Burger, Dara M. Cannon, M. Mallar Chakravarty, Qiang Chen, John Tsun Po Cheung, Baptiste Couvy‐Duchesne, Anders Martin 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 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 Pedersen Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. 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, Thomas Matthew Lancaster, Phil H. Lee, Tristram A. P. Lett, Lindsay B. Lewis, Íscia Lopes‐Cendes, Michelle Luciano, Fabio M. Macciardi, André F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza‐Schreiber, José C.V. Moreira, Thomas W. Mühleisen, Bertram Müller‐Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik T. 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 Sonja 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 Elken Sønderby, Emma Sprooten, Katherine E. Tansey, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas‐Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza Ludovica 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 Herman Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang, Yunpeng Wang, Joanna Marguerite Wardlaw, Wei Wen, Lars Tjelta Westlye, Christopher D. Whelan, Stephanie H. Witt, Katharina Wittfeld, Christiane Wolf, Thomas Wolfers, Jing Qin Wu, Clarissa Lin Yasuda, Dario Zaremba, Zuo Zhang, Marcel P. Zwiers, Éric Artiges, Amelia A. Assareh, Rosa Ayesa‐Arriola, Ayşenil Belger, Christine Lycke 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 Anne Gowland, Robert C. Green, Alexander Niklas Häusler, Walter Leonhard Heindel, Beng‐Choon Ho, Wolfgang U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, MiHyun Jang, Andreas Jansen, Nathan A. Kimbrel, Knut K. Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen Justin Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews, Jacqueline Mayoral-van Son, Sarah C McEwen, Ingrid S. Melle, Derek W. Morris, Bryon A. Mueller, Matthias A. Nauck, Jan Egil Nordvik, Markus Maria Nöthen, Daniel S. OʼLeary, Nils Opel, Marie‐Laure Paillère Martinot, G. Bruce Pike, Adrian Preda, Erin Burke Quinlan, Paul E. Rasser, Varun Ratnakar, Simone Reppermund, Vidar Martin Steen, Paul A. Tooney, Fábio R. Torres, Dick J. Veltman, James Voyvodic, Robert Whelan, Tonya J.H. White, Hidenaga Yamamori, Hieab H.H. Adams, Joshua C. Bis, Stéphanie Debette, Charles S DeCarli, Myriam Fornage, Vilmundur G. Gudnason, Edith Hofer, M. Arfan Ikram, Lenore J. Launer, William T. Longstreth Jr., Oscar L. López, Bernard M. Mazoyer, Thomas H. Mosley, Gennady V. Roshchupkin, Claudia Liliana Satizábal, Reinhold Schmidt, Sudha S. Seshadri, Qiong Yang, Alzheimer’s Disease Neuroimaging Initiative¶, Parkinson’s Progression Markers Initiative¶, Marina K. M. Alvim, David Ames, Tim Anderson, Ole A. Andreassen, Alejandro Arias Vásquez, Mark E. Bastin, Bernhard Theodor Baune, Jean C. Beckham, John Blangero, Dorret Irene Boomsma, Henry Brodaty, Han G. Brunner, Randy Lee Buckner, Jan K. Buitelaar, Juan Bustillo, Wiepke Cahn, Murray J. Cairns, Vince D. Calhoun, Vaughan J. Carr, Xavier Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando Cendes, Aiden P. 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 J Donohoe, Thomas Espeseth, Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Hans Jörgen Grabe, Oliver Gruber, Asta Kristine Haberg, Ahmad R. Hariri, Catharina Annette Hartman, Ryota Hashimoto, Andreas Heinz, Frans Alexander Henskens, Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, Liyi Elliot Hong, William Donald Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik Gunnar Jönsson, René S. Kahn, Martin Alexander Kennedy, Tilo T. J. Kircher, Peter V Kochunov, John B. Kwok, Stéphanie Le Hellard, Carmel Maree Loughland, Nicholas G. Martin, Jean‐Luc Martinot, Colm McDonald, Katie Louise McMahon, Andreas Meyer‐Lindenberg, Patricia Therese Michie, Rajendra A. Morey, Bryan J. Mowry, Lars H Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Christos Pantelis, Tomáš Paus, Zdenka Pausová, Brenda W.J.H. Penninx, Tinca J. C. Polderman, Daniëlle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Perminder Singh Sachdev, Philipp Gero Sämann, Ulrich Schall, Günter Schumann, Rodney J. Scott, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beaté St Pourcain, Dan J. Stein, Arthur W. Toga, Julian Norman Trollor, Nic J.A. van der Wee, Dennis van ‘t Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Helen Zhou, Jason L. Stein, Paul M. Thompson, Sarah Elizabeth Medland · 发表于：Science · 年份：2020 · DOI：10.1126/science.aay6690 · 被引用次数：910 · 研究领域：Genetic Associations and Epidemiology、Epigenetics and DNA Methylation、Bioinformatics and Genomic Networks

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 369 nominally genome-wide significant loci ( P < 5 × 10 −8 ) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P < 8.3 × 10 −10 ; 187 influencing surface area and 50 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation ( r G = −0.32, SE = 0.0...