The genetic architecture of the human cerebral cortex

Author:

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,Atkins Joshua R.,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.,den Braber Anouk,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.,Green Melissa J.,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,Quidé Yann,Ragothaman Anjanibhargavi,Rashid Faisal M.,Reay William R.,Redlich Ronny,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,van der Meer Dennis,van Donkelaar Marjolein M.J.,van Eijk Liza,van Erp Theo G.M.,van Haren Neeltje E.M.,van Rooij Daan,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,Wu Jing Qin,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,Dennis Michelle F.,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,Kimbrel Nathan A.,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.,Rasser Paul E.,Ratnakar Varun,Reppermund Simone,Steen Vidar M.,Tooney Paul A.,Torres Fábio R.,Veltman Dick J.,Voyvodic James T.,Whelan Robert,White Tonya,Yamamori Hidenaga,Lopez Oscar L.,Adams Hieab H.H.,Bis Joshua C.,Debette Stephanie,Decarli Charles,Fornage Myriam,Gudnason Vilmundur,Hofer Edith,Ikram M. Arfan,Launer Lenore,Longstreth W. T.,Mazoyer Bernard,Mosley Thomas H.,Roshchupkin Gennady V.,Satizabal Claudia L.,Schmidt Reinhold,Seshadri Sudha,Yang Qiong,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,Cairns Murray J.,Calhoun Vince,Carr Vaughan J.,Caseras Xavier,Caspers Svenja,Cavalleri Gianpiero L.,Cendes Fernando,Crespo-Facorro Benedicto,Dalrymple-Alford John C.,Dannlowski Udo,de Geus Eco J.C.,Deary Ian J.,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,Henskens Frans A.,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,Loughland Carmel M.,Martin Nicholas G.,Martinot Jean-Luc,McDonald Colm,McMahon Katie L.,Meyer-Lindenberg Andreas,Michie Patricia T.,Morey Rajendra A.,Mowry Bryan,Nyberg Lars,Oosterlaan Jaap,Ophoff Roel A.,Pantelis Christos,Paus Tomas,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.,Schall Ulrich,Schumann Gunter,Scott Rodney J.,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.,van ‘t Ent Dennis,Völzke Henry,Walter Henrik,Weber Bernd,Weinberger Daniel R.,Wright Margaret J.,Zhou Juan,Stein Jason L.,Thompson Paul M.,Medland Sarah E., , , , , , ,

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P≤ 5 × 10−8); 199 survived multiple testing correction (P≤ 8.3 × 10−10; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression and ADHD.One Sentence SummaryCommon genetic variation is associated with inter-individual variation in the structure of the human cortex, both globally and within specific regions, and is shared with genetic risk factors for some neuropsychiatric disorders.

Publisher

Cold Spring Harbor Laboratory

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