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The genetic architecture of the human cerebral cortex
Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro‐Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R. K. Ching, Mary McMahon, Natalia Shatokhina, Leo Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison E. Ashley‐Koch, Joshua Atkins, Manon Bernard, Rachel M. Brouwer, Elizabeth E.L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, M. Mallar Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy‐Duchesne, Anders M. 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 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 P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc 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, T. Lancaster, Phil H. Lee, Tristram A. Lett, Lindsay B. Lewis, Íscia Lopes‐Cendes, Michelle Luciano, 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, Loes M. Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Yann Quidé, Anjanibhargavi Ragothaman, Faisal Rashid, William R. Reay, Ronny Redlich, 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, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E. Tansey, Alexander Teumer, Anbupalam Thalamuthu, 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, Wei Wen, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Katharina Wittfeld, Christiane Wolf, Thomas Wolfers, Jing Wu, 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, 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 Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng‐Choon Ho, Wolfgang 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 J. Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews, Sarah McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias Nauck, Jan Egil Nordvik, Markus M. 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 M. Steen, Paul A. Tooney, Fábio R. Torres, Dick J. Veltman, James Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Oscar L. Lopez, Hieab H.H. Adams, Joshua C. Bis, Stéphanie Debette, Charles DeCarli, Myriam Fornage, Vilmundur Guðnason, Edith Hofer, M. Arfan Ikram, Lenore J. Launer, W.T. Longstreth, Bernard Mazoyer, Thomas H. Mosley, Gennady V. Roshchupkin, Claudia L. Satizábal, Reinhold Schmidt, Sudha Seshadri, Qiong Yang, Marina K. M. Alvim, David Ames, Tim Anderson, Ole A. Andreassen, Alejandro Arias Vásquez, Mark E. Bastin, Bernhard T. Baune, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner, Randy L. 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, Benedicto Crespo‐Facorro, John C. Dalrymple‐Alford, Udo Dannlowski, Eco J. C. de Geus, Ian J. Deary, 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, Hans J. Grabe, Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Frans Henskens, 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 Kircher, Peter Kochunov, John B. Kwok, Stéphanie Le Hellard, Carmel M. Loughland, Nicholas G. Martin, Jean‐Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer‐Lindenberg, Patricia T. Michie, Rajendra A. Morey, Bryan Mowry, Lars 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 S. Sachdev, Philipp G. 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 N. Trollor, Nic J.A. van der Wee, Dennis van ‘t Ent, Henry Völzke, Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Zhou, Jason L. Stein, Paul M. Thompson, Sarah E. Medland
Bibliographic record
VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsHolland Bloorview Kids Rehabilitation HospitalUniversity of CalgaryMcGill UniversityDouglas Mental Health University InstituteMontreal Neurological Institute and HospitalUniversity of TorontoSickKids FoundationHospital for Sick Children
FundersFP7 Ideas: European Research CouncilNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Human Genome Research InstituteHelmholtz Zentrum MünchenNational Health and Medical Research CouncilAustralian Research CouncilBiotechnology and Biological Sciences Research CouncilMedical Research CouncilHorizon 2020 Framework ProgrammeUniversity of California, IrvineUniversity of California, San FranciscoQueensland Brain InstituteUniversity of California, San DiegoUniversity of California, DavisDirectorate for Biological SciencesNational Institutes of HealthMax Planck Instituut voor PsycholinguïstiekDementia Centre for Research CollaborationUniversity of California, Los AngelesAvera Institute for Human GeneticsMacquarie Group FoundationNational Institute on AgingUniversität GreifswaldEpilepsy SocietyInstituut Born-BungeStiftelsen Konsul Thure Carlssons MinneCentre for Cognitive Ageing and Cognitive EpidemiologyRamsay Health CareMinistry of Cultural AffairsVlaamse regeringAlzheimer NederlandNational Healthcare GroupNational Institute of Biomedical Imaging and BioengineeringNovo Nordisk FondenUniversity College London Hospitals NHS Foundation TrustMutuelle Générale de l'Education NationaleUniversiteit AntwerpenSwedish Brain PowerBergens ForskningsstiftelseUniversidade Estadual de CampinasUniversité de BordeauxUniversitetet i OsloNational Center for PTSD, U.S. Department of Veterans AffairsDeutsches Zentrum für Neurodegenerative ErkrankungenUniversitair Medisch Centrum GroningenUniversitetet i BergenHelse Midt-NorgeNational Medical Research CouncilNorges ForskningsrådStockholms Läns LandstingVetenskapsrådetNovo NordiskHelse Sør-Øst RHFMax-Planck-GesellschaftOesterreichische NationalbankKarolinska InstitutetUniversity of TorontoMaryland Population Research Center, University of MarylandMinistero dell’Istruzione, dell’Università e della RicercaAccareNederlandse Organisatie voor Wetenschappelijk OnderzoekFonds Wetenschappelijk OnderzoekSiemens HealthineersInnovative Medicines InitiativeFondation pour la Recherche MédicaleFondazione CariploKing Faisal Specialist Hospital and Research CentreRadboud UniversiteitCompute CanadaRussian Foundation for Basic ResearchVrije Universiteit AmsterdamNorges Teknisk-Naturvitenskapelige UniversitetUniversiteit UtrechtTechnische Universiteit DelftZonMwNational Institute of Mental HealthCase Western Reserve UniversityUSF Health Byrd Alzheimer's InstituteUniversity of SydneyJohns Hopkins UniversityWellcome TrustAgence Nationale de la RechercheMurdoch UniversityDeutsche ForschungsgemeinschaftUniversity of GalwayCardiff UniversityFundação de Amparo à Pesquisa do Estado de São PauloCanadian Institutes of Health ResearchKnut och Alice Wallenbergs StiftelseEuropean CommissionBrown UniversityNewcastle UniversityNIHR Cambridge Biomedical Research CentreMassachusetts General HospitalUniversity College LondonJewish General HospitalAustrian Science FundUniversity of QueenslandNational Institute for Health and Care ResearchAlzheimer's Research TrustGillings School of Public HealthAlzheimer's SocietyKing's College LondonLieber Institute for Brain DevelopmentMinistero della SaluteEuropean Federation of Pharmaceutical Industries and AssociationsInstitut National de la Santé et de la Recherche MédicaleGovernment of OntarioLeids Universitair Medisch CentrumSanofiNeuroscience Research AustraliaYale UniversityUniversity of Texas Health Science Center at HoustonPratt FoundationFoundation for the National Institutes of HealthNational Alliance for Research on Schizophrenia and DepressionDartmouth CollegeBelgian Federal Science Policy OfficeAlbert Einstein College of Medicine, Yeshiva UniversityUniversity of South FloridaBrain and Behavior Research FoundationMcGill UniversityU.S. Department of Veterans AffairsU.S. Department of EnergyHarvard T.H. Chan School of Public HealthFondation pour la Recherche sur AlzheimerRadboud Universitair Medisch CentrumUniversity of New South WalesMedical Center, University of RochesterUniversity of PittsburghWake Forest UniversityDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseYork UniversityFondation de l'Avenir pour la Recherche Médicale AppliquéeEU Joint Programme – Neurodegenerative Disease ResearchCentre National de la Recherche ScientifiquePfizerUniversity of WashingtonNational Heart, Lung, and Blood InstituteOhio State UniversityUniversiteit LeidenCleveland ClinicHospital for Sick ChildrenSchool of Medicine, Boston UniversityNorthwestern UniversityTrinity College DublinCurePSPKarl-Franzens-Universität GrazSvenska Forskningsrådet FormasMetLife FoundationEli Lilly and CompanyInstituto de Investigación Marqués de ValdecillaStichting DioraphteMedizinische Universität GrazTexas Tech UniversitySylvia and Charles Viertel Charitable FoundationFondation de FranceUniversity of PennsylvaniaVirginia Commonwealth UniversityNational Center for Advancing Translational SciencesBundesministerium für Bildung und ForschungStanley Medical Research InstituteAge UKUniversity of Southern CaliforniaEmory UniversityAlzheimer's AssociationHersenstichtingU.S. Department of DefenseBrigham and Women's HospitalU.S. Department of Health and Human ServicesGlaxoSmithKlineUniversity of RochesterHeart and Stroke Foundation of CanadaNIHR Newcastle Biomedical Research CentreMission Interministérielle de Lutte Contre les Drogues et les Conduites AddictivesFondation LeducqNational Science FoundationCenter of Excellence for Stress and Mental HealthYeshiva UniversityRush UniversityGeorgetown UniversityScience Foundation IrelandFondazione Cassa di Risparmio di Pistoia e Pescia
KeywordsCortex (anatomy)Human brainBiologyNeuroscienceGenetic architectureCerebral cortexCognitionEvolutionary biologyGeneticsGeneQuantitative trait locus
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 Summary Common 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.014
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.009
GPT teacher head0.228
Teacher spread0.218 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations42
Published2018
Admission routes2
Has abstractyes