Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium
Edith Hofer(Medical University of Graz), Gennady V. Roshchupkin(Erasmus MC), Hieab H.H. Adams(Erasmus MC), Maria J. Knol(Erasmus MC), Honghuang Lin(Boston University), Shuo Li(Boston University), Habil Zare(The University of Texas at San Antonio Health Science Center), Shahzad Ahmad(Erasmus MC), Nicola J. Armstrong(Murdoch University), Claudia L. Satizábal(Institute for Neurodegenerative Disorders), Manon Bernard(Hospital for Sick Children), Joshua C. Bis(University of Washington), Nathan A. Gillespie(Virginia Commonwealth University), Michelle Luciano(University of Edinburgh), Aniket Mishra(Université de Bordeaux), Markus Scholz(Leipzig University), Alexander Teumer(Universitätsmedizin Greifswald), Rui Xia(The University of Texas Health Science Center at Houston), Xueqiu Jian(The University of Texas Health Science Center at Houston), Thomas H. Mosley(Jackson Memorial Hospital), Yasaman Saba(Medical University of Graz), Lukas Pirpamer(Medical University of Graz), Stephan Seiler(University of California, Davis), James T. Becker(University of Pittsburgh), Owen Carmichael(Pennington Biomedical Research Center), Jerome I. Rotter(The Lundquist Institute), Bruce M. Psaty(University of Washington), Oscar L. Lopez(University of Pittsburgh), Najaf Amin(Erasmus MC), Sven J. van der Lee(Erasmus MC), Qiong Yang(Boston University), Jayandra J. Himali(Boston University), Pauline Maillard(University of California, Davis), Alexa Beiser(Boston University), Charles DeCarli(University of California, Davis), Sherif Karama(Montreal Neurological Institute and Hospital), Lindsay B. Lewis(Montreal Neurological Institute and Hospital), Mathew A. Harris(University of Edinburgh), Mark E. Bastin(University of Edinburgh), Ian J. Deary(University of Edinburgh), A. Veronica Witte(Max Planck Institute for Human Cognitive and Brain Sciences), Frauke Beyer(Max Planck Institute for Human Cognitive and Brain Sciences), Markus Loeffler(Leipzig University), Karen A. Mather(UNSW Sydney), Peter R. Schofield(UNSW Sydney), Anbupalam Thalamuthu(UNSW Sydney), John B. Kwok(The University of Sydney), Margaret J. Wright(The University of Queensland), David Ames(The Royal Melbourne Hospital), Julian N. Trollor(UNSW Sydney), Jiyang Jiang(UNSW Sydney), Henry Brodaty(UNSW Sydney), Wei Wen(UNSW Sydney), Meike W. Vernooij(Erasmus MC), Albert Hofman(Harvard University), André G. Uitterlinden(Erasmus MC), Wiro J. Niessen(Erasmus MC), Katharina Wittfeld(Universitätsmedizin Greifswald), Robin Bülow(Universitätsmedizin Greifswald), Uwe Völker(Universitätsmedizin Greifswald), Zdenka Pausová(University of Toronto), G. Bruce Pike(University of Calgary), Sophie Maingault(Centre National de la Recherche Scientifique), Fabrice Crivello(Centre National de la Recherche Scientifique), Christophe Tzourio(Université de Bordeaux), Philippe Amouye(Inserm), Bernard Mazoyer(Centre National de la Recherche Scientifique), Michael C. Neale(Virginia Commonwealth University), Carol E. Franz(University of California San Diego), Michael J. Lyons(Boston University), Matthew S. Panizzon(University of California San Diego), Ole A. Andreassen(Oslo University Hospital), Anders M. Dale(University of California San Diego), Mark Logue(Boston University), Katrina L. Grasby(QIMR Berghofer Medical Research Institute), Neda Jahanshad(University of Southern California), Jodie N. Painter(QIMR Berghofer Medical Research Institute), Lucía Colodro‐Conde(QIMR Berghofer Medical Research Institute), Janita Bralten(Radboud University Nijmegen), Derrek P. Hibar(University of Southern California), Penelope A. Lind(QIMR Berghofer Medical Research Institute), Fabrizio Pizzagalli(University of Southern California), Jason L. Stein(University of North Carolina at Chapel Hill), Paul M. Thompson(University of Southern California), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Katrina L. Grasby(QIMR Berghofer Medical Research Institute), Neda Jahanshad(University of Southern California), Jodie N. Painter(QIMR Berghofer Medical Research Institute), Lucía Colodro‐Conde(QIMR Berghofer Medical Research Institute), Janita Bralten(Radboud University Nijmegen), Derrek P. Hibar(University of Southern California), Penelope A. Lind(QIMR Berghofer Medical Research Institute), Fabrizio Pizzagalli(University of Southern California), R.K. Ching Christopher(Boston University), Bouchez Agnes(University of Southern California), Natalia Shatokhina, Leo Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard(Centre National de la Recherche Scientifique), Nicola J. Armstrong(Murdoch University), Allison E. Ashley‐Koch, Manon Bernard(Hospital for Sick Children), Rachel M. Brouwer, Elizabeth E.L. Buimer, Robin Bülow(Universitätsmedizin Greifswald), Christian Bürger, Dara M. Cannon, M. Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy‐Duchesne, Anders M. Dale(University of California San Diego), Shareefa Dalvie, Tânia Kawasaki de Araujo, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm(Universitätsmedizin Greifswald), Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan(Erasmus MC), Iryna O. Fedko, Sonya Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge(Erasmus MC), Sudheer Giddaluru, Aaron L. Goldman, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris(University of Edinburgh), Marc Harrison, Courtney C. Haswell, Michael A. Hauser(Boston University), Stefan Herms, Dirk J. Heslenfeld, New Fei Ho(University of Southern California), David Hoehn(The Royal Melbourne Hospital), Per Hoffmann, Laurena Holleran, Martine Hoogman, Jouke‐Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris E. Jansen, Tianye Jia(UNSW Sydney), Christiane Jockwitz, Ryota Kanai, Sherif Karama(Montreal Neurological Institute and Hospital), Dalia Kasperavičiūtė, Tobias Kaufmann, Sinéad Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp(Boston University), Annchen R. Knodt, Bernd Krämer, Max Lam(UNSW Sydney), T. Lancaster(University of Mississippi Medical Center), Phil H. Lee(Erasmus MC), Tristram A. Lett, Lindsay B. Lewis(Montreal Neurological Institute and Hospital), Íscia Lopes‐Cendes, Michelle Luciano(University of Edinburgh), Fabìo 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 Nho(Medical University of Graz), Loes M. Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Anjanibhargavi Ragothaman, Faisal Rashid, Redlich Ronny, 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(UNSW Sydney), Rodrigo Secolin, Chin Yang Shapland, Li Shen(University of Southern California), Jean Shin, Elena Shumskaya(Medical University of Graz), Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E. Tansey, Alexander Teumer(Universitätsmedizin Greifswald), Anbupalam Thalamuthu(UNSW Sydney), 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(University of Edinburgh), Wei Wen(UNSW Sydney), Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt(Universitätsmedizin Greifswald), Katharina Wittfeld(Universitätsmedizin Greifswald), Christiane Wolf, Thomas Wolfers(Jackson Memorial Hospital), 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(Erasmus MC), Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil(Virginia Commonwealth University), Penny Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng‐Choon Ho(University of Southern California), Wolfgang Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack, MiHyun Jang, Andreas Jansen(Oslo University Hospital), Knut K. Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim, Jurjen J. Luykx, Daniel H. Mathalon, Karen A. Mather(UNSW Sydney), Venkata S. Mattay, Sarah Matthews(University of California San Diego), 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(QIMR Berghofer Medical Research Institute), Marie‐Laure Paillère Martinot, G. Bruce Pike(University of Calgary), Adrian Preda, Erin Burke Quinlan, Varun Ratnakar, Simone Reppermund, Vidar M. Steen, Fábio R. Torres, Dick J. Veltman, James Voyvodic(University of Pittsburgh), Robert Whelan, Tonya White, Hidenaga Yamamori, Marina K. M. Alvim, David Ames(The Royal Melbourne Hospital), Tim Anderson, Ole A. Andreassen(Oslo University Hospital), Alejandro Arias Vásquez, Mark E. Bastin(University of Edinburgh), Bernhard T. Baune, John Blangero(The University of Sydney), Dorret I. Boomsma, Henry Brodaty(UNSW Sydney), Han G. Brunner(Virginia Commonwealth University), 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(University of Edinburgh), Norman Delanty, Chantal Depondt, Sylvane Desrivières, Gary Donohoe, Thomas Espeseth(Jackson Memorial Hospital), Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Hans J. Grabe(Universitätsmedizin Greifswald), Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz(Oslo University Hospital), Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong(Boston University), William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo Kircher, Peter Kochunov(UNSW Sydney), John B. Kwok(The University of Sydney), Stéphanie Le Hellard, Nicholas G. Martin, Jean Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer‐Lindenberg(Oslo University Hospital), Rajendra A. Morey, Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Tomáš Paus(University of Toronto), Zdenka Pausová(University of Toronto), Brenda W.J.H. Penninx, Tinca J. C. Polderman, Daniëlle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland, Perminder S. Sachdev(UNSW Sydney), Philipp G. Sämann, Gunter Schumann, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beaté St Pourcain, Dan J. Stein(University of North Carolina at Chapel Hill), Arthur W. Toga, Julian N. Trollor(UNSW Sydney), Nic J.A. van der Wee, Dennis van ‘t Ent, Henry Völzke(UNSW Sydney), Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright(The University of Queensland), Juan Zhou, Jason L. Stein(University of North Carolina at Chapel Hill), Paul M. Thompson(University of Southern California), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Faisal Rashid, Perminder S. Sachdev(UNSW Sydney), William S. Kremen(University of California San Diego), Joanna M. Wardlaw(University of Edinburgh), Arno Villringer(University Hospital Leipzig), Cornelia M. van Duijn(Erasmus MC), Hans J. Grabe(University of Southern California), W.T. Longstreth(University of Washington), Myriam Fornage(The University of Texas Health Science Center at Houston), Tomáš Paus(University of Toronto), Stéphanie Debette(Boston University), M. Arfan Ikram(Erasmus MC), Helena Schmidt(Medical University of Graz), Reinhold Schmidt(Medical University of Graz), Sudha Seshadri
Cited by 25Open Access
Abstract
Abstract Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was 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.
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