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

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. Satizabal, Manon Bernard, Joshua C. Bis, Nathan A. Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas H. MosleyYasaman 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 S. Beiser, Charles Decarli, Sherif Karama, Lindsay Lewis, Mat 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 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 Pausova, 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 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, Perminder S. Sachdev, William S. Kremen, Joanna M. Wardlaw, Arno Villringer, Cornelia M. van Duijn, Hans J. Grabe, William T. Longstreth, Myriam Fornage, Tomas Paus, Stephanie Debette, M. Arfan Ikram, Helena Schmidt, Reinhold Schmidt, Sudha Seshadri, Christopher R.K. Ching, Mary Agnes B. McMahon, Natalia Shatokhina, Leo C.P. Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio A.A. Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Allison Ashley-Koch, Rachel M. Brouwer, Elizabeth E.L. Buimer, Christian Bürger, Dara M. Cannon, Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-Duchesne, Shareefa Dalvie, Tânia K. 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, 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, 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, Iscia Lopes-Cendes, Fabio Macciardi, Andre F. Marquand, Samuel R. Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C.V. 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 M. Rashid, 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, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E. Tansey, Sophia I. Thomopoulos, 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 H. Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang, Yunpeng Wang, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Christiane Wolf, Thomas Wolfers, 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, 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, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen J. Luykx, Daniel H. Mathalon, 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, Adrian Preda, Erin B. 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, Tim J. Anderson, Alejandro Arias-Vasquez, Bernhard T. Baune, John Blangero, Dorret I. Boomsma, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Vince 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, 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, 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 T.J. Kircher, Peter Kochunov, Stephanie 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, Brenda W.J.H. Penninx, Tinca J.C. Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Philipp G. Sämann, Gunter Schumann, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Arthur W. Toga, Nic J.A. Van der Wee, Dennis Van’T Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Juan Zhou

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number4796
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Sep 22 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging/genetics
  • Brain
  • Chromosome Structures
  • Cognition
  • Female
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Male
  • Mental Disorders/genetics
  • Middle Aged
  • Neurodegenerative Diseases/genetics
  • Phenotype
  • Polymorphism, Single Nucleotide

PubMed: MeSH publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Meta-Analysis
  • Journal Article
  • Research Support, N.I.H., Extramural

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