Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium
Authors: Hofer Edith , Roshchupkin Gennady V. , Adams Hieab H. H. , Knol Maria J. , Lin Honghuang , Li Shuo , Zare Habil , Ahmad Shahzad , Armstrong Nicola J. , Satizabal Claudia L. , Bernard Manon , Bis Joshua C. , Gillespie Nathan A. , Luciano Michelle , Mishra Aniket , Scholz Markus , Teumer Alexander , Xia Rui , Jian Xueqiu , Mosley Thomas H. , Saba Yasaman , Pirpamer Lukas , Seiler Stephan , Becker James T. , Carmichael Owen , Rotter Jerome I. , Psaty Bruce M. , Lopez Oscar L. , Amin Najaf , van der Lee Sven J. , Yang Qiong , Himali Jayandra J. , Maillard Pauline , Beiser Alexa S. , DeCarli Charles , Karama Sherif , Lewis Lindsay , Harris Mat , Bastin Mark E. , Deary Ian J. , Witte A.Veronica , Beyer Frauke , Loeffler Markus , Mather Karen A. , Schofield Peter R. , Thalamuthu Anbupalam , Kwok John B. , Wright Margaret J. , Ames David , Trollor Julian , Jiang Jiyang , Brodaty Henry , Wen Wei , Vernooij Meike W , Hofman Albert , Uitterlinden André G. , Niessen Wiro J. , Wittfeld Katharina , Bülow Robin , Völker Uwe , Pausova Zdenka , Pike G. Bruce , Maingault Sophie , Crivello Fabrice , Tzourio Christophe , Amouye Philippe , Mazoyer Bernard , Neale Michael C. , Franz Carol E. , Lyons Michael J. , Panizzon Matthew S. , Andreassen Ole A. , Dale Anders M. , Logue Mark , Grasby Katrina L. , Jahanshad Neda , Painter Jodie N. , Colodro-Conde Lucía , Bralten Janita , Hibar Derrek P. , Lind Penelope A. , Pizzagalli Fabrizio , Stein Jason L. , Thompson Paul M. , Medland Sarah E. ,   ENIGMA consortium, Grasby Katrina L. , Jahanshad Neda , Painter Jodie N. , Colodro-Conde Lucía , Bralten Janita , Hibar Derrek P. , Lind Penelope A. , Pizzagalli Fabrizio , Ching Christopher R.K. , McMahon Mary Agnes B. , Shatokhina Natalia , Zsembik Leo C.P. , Agartz Ingrid , Alhusaini Saud , Almeida Marcio A.A. , Alnæs Dag , Amlien Inge K. , Andersson Micael , Ard Tyler , Armstrong Nicola J. , Ashley-Koch Allison , Bernard Manon , Brouwer Rachel M. , Buimer Elizabeth E.L. , Bülow Robin , Bürger Christian , Cannon Dara M. , Chakravarty Mallar , Chen Qiang , Cheung Joshua W. , Couvy-Duchesne Baptiste , Dale Anders M. , Dalvie Shareefa , de Araujo Tânia K. , de Zubicaray Greig I. , de Zwarte Sonja M.C. , Braber Anouk den , Doan Nhat Trung , Dohm Katharina , Ehrlich Stefan , Engelbrecht Hannah-Ruth , Erk Susanne , Fan Chun Chieh , Fedko Iryna O. , Foley Sonya F. , Ford Judith M. , Fukunaga Masaki , Garrett Melanie E. , Ge Tian , Giddaluru Sudheer , Goldman Aaron L. , Groenewold Nynke A. , Grotegerd Dominik , Gurholt Tiril P. , Gutman Boris A. , Hansell Narelle K. , Harris Mathew A. , Harrison Marc B. , Haswell Courtney C. , Hauser Michael , Herms Stefan , Heslenfeld Dirk J. , Ho New Fei , Hoehn David , Hoffmann Per , Holleran Laurena , Hoogman Martine , Hottenga Jouke-Jan , Ikeda Masashi , Janowitz Deborah , Jansen Iris E. , Jia Tianye , Jockwitz Christiane , Kanai Ryota , Karama Sherif , Kasperaviciute Dalia , Kaufmann Tobias , Kelly Sinead , Kikuchi Masataka , Klein Marieke , Knapp Michael , Knodt Annchen R. , Krämer Bernd , Lam Max , Lancaster Thomas M. , Lee Phil H. , Lett Tristram A. , Lewis Lindsay B. , Lopes-Cendes Iscia , Luciano Michelle , Macciardi Fabio , Marquand Andre F. , Mathias Samuel R. , Melzer Tracy R. , Milaneschi Yuri , Mirza-Schreiber Nazanin , Moreira Jose C.V. , Mühleisen Thomas W. , Müller-Myhsok Bertram , Najt Pablo , Nakahara Soichiro , Nho Kwangsik , Olde Loohuis Loes M. , Orfanos Dimitri Papadopoulos , Pearson John F. , Pitcher Toni L. , Pütz Benno , Ragothaman Anjanibhargavi , Rashid Faisal M. , Ronny Redlich , Reinbold Céline S. , Repple Jonathan , Richard Geneviève , Riedel Brandalyn C. , Risacher Shannon L. , Rocha Cristiane S. , Mota Nina Roth , Salminen Lauren , Saremi Arvin , Saykin Andrew J. , Schlag Fenja , Schmaal Lianne , Schofield Peter R. , Secolin Rodrigo , Shapland Chin Yang , Shen Li , Shin Jean , Shumskaya Elena , Sønderby Ida E. , Sprooten Emma , Strike Lachlan T. , Tansey Katherine E. , Teumer Alexander , Thalamuthu Anbupalam , Thomopoulos Sophia I. , Tordesillas-Gutiérrez Diana , Turner Jessica A. , Uhlmann Anne , Vallerga Costanza Ludovica , der Meer Dennis van , van Donkelaar Marjolein M.J. , Eijk Liza van , van Erp Theo G.M. , van Haren Neeltje E.M. , Rooij Daan van , van Tol Marie-José , Veldink Jan H. , Verhoef Ellen , Walton Esther , Wang Mingyuan , Wang Yunpeng , Wardlaw Joanna M. , Wen Wei , Westlye Lars T. , Whelan Christopher D. , Witt Stephanie H. , Wittfeld Katharina , Wolf Christiane , Wolfers Thomas , Yasuda Clarissa L. , Zaremba Dario , Zhang Zuo , Zhu Alyssa H. , Zwiers Marcel P. , Artiges Eric , Assareh Amelia A. , Ayesa-Arriola Rosa , Belger Aysenil , Brandt Christine L. , Brown Gregory G. , Cichon Sven , Curran Joanne E. , Davies Gareth E. , Degenhardt Franziska , Dietsche Bruno , Djurovic Srdjan , Doherty Colin P. , Espiritu Ryan , Garijo Daniel , Gil Yolanda , Gowland Penny A. , Green Robert C. , Häusler Alexander N. , Heindel Walter , Ho Beng-Choon , Hoffmann Wolfgang U. , Holsboer Florian , Homuth Georg , Hosten Norbert , Jack Clifford R. , Jang MiHyun , Jansen Andreas , Kolskår Knut , Koops Sanne , Krug Axel , Lim Kelvin O. , Luykx Jurjen J. , Mathalon Daniel H. , Mather Karen A. , Mattay Venkata S. , Matthews Sarah , Van Son Jaqueline Mayoral , McEwen Sarah C. , Melle Ingrid , Morris Derek W. , Mueller Bryon A. , Nauck Matthias , Nordvik Jan E. , Nöthen Markus M. , O’Leary Daniel S. , Opel Nils , Paillère Martinot Marie-Laure , Pike G. Bruce , Preda Adrian , Quinlan Erin B. , Ratnakar Varun , Reppermund Simone , Steen Vidar M. , Torres Fábio R. , Veltman Dick J. , Voyvodic James T. , Whelan Robert , White Tonya , Yamamori Hidenaga , Alvim Marina K.M. , Ames David , Anderson Tim J. , Andreassen Ole A. , Arias-Vasquez Alejandro , Bastin Mark E. , Baune Bernhard T. , Blangero John , Boomsma Dorret I. , Brodaty Henry , Brunner Han G. , Buckner Randy L. , Buitelaar Jan K. , Bustillo Juan R. , Cahn Wiepke , Calhoun Vince , Caseras Xavier , Caspers Svenja , Cavalleri Gianpiero L. , Cendes Fernando , Corvin Aiden , Crespo-Facorro Benedicto , Dalrymple-Alford John C. , Dannlowski Udo , de Geus Eco J.C. , Deary Ian J. , Delanty Norman , Depondt Chantal , Desrivières Sylvane , Donohoe Gary , Espeseth Thomas , Fernández Guillén , Fisher Simon E. , Flor Herta , Forstner Andreas J. , Francks Clyde , Franke Barbara , Glahn David C. , Gollub Randy L. , Grabe Hans J. , Gruber Oliver , Håberg Asta K. , Hariri Ahmad R. , Hartman Catharina A. , Hashimoto Ryota , Heinz Andreas , Hillegers Manon H.J. , Hoekstra Pieter J. , Holmes Avram J. , Hong L. Elliot , Hopkins William D. , Hulshoff Pol Hilleke E. , Jernigan Terry L. , Jönsson Erik G. , Kahn René S. , Kennedy Martin A. , Kircher Tilo T.J. , Kochunov Peter , Kwok John B.J. , Hellard Stephanie Le , Martin Nicholas G. , Martinot Jean - Luc , McDonald Colm , McMahon Katie L. , Meyer-Lindenberg Andreas , Morey Rajendra A. , Nyberg Lars , Oosterlaan Jaap , Ophoff Roel A. , Paus Tomáš , Pausova Zdenka , Penninx Brenda W.J.H. , Polderman Tinca J.C. , Posthuma Danielle , Rietschel Marcella , Roffman Joshua L. , Rowland Laura M. , Sachdev Perminder S. , Sämann Philipp G. , Schumann Gunter , Sim Kang , Sisodiya Sanjay M. , Smoller Jordan W. , Sommer Iris E. , Pourcain Beate St , Stein Dan J. , Toga Arthur W. , Trollor Julian N. , Van der Wee Nic J.A. , Ent Dennis van’t , Völzke Henry , Walter Henrik , Weber Bernd , Weinberger Daniel R. , Wright Margaret J. , Zhou Juan , Stein Jason L. , Thompson Paul M. , Medland Sarah E. , Rashid Faisal M. , Sachdev Perminder S. , Kremen William S. , Wardlaw Joanna M. , Villringer Arno , Duijn Cornelia M. van , Jörgen Grabe Hans , Longstreth William T. , Fornage Myriam , Paus Tomas , Debette Stephanie , Ikram M. Arfan , Schmidt Helena , Schmidt Reinhold , Seshadri Sudha 
Published: September 2018

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.