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Record W2752955499 · doi:10.1101/173831

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

2017· preprint· en· W2752955499 on OpenAlexaff
Claudia L. Satizábal, Hieab H.H. Adams, Derrek P. Hibar, Charles C. White, Jason L. Stein, Markus Scholz, Muralidharan Sargurupremraj, Neda Jahanshad, Albert V. Smith, Xueqiu Jian, Michelle Luciano, Edith Hofer, Alexander Teumer, Sven J. van der Lee, Jingyun Yang, Lisa R. Yanek, Tom V. Lee, Shuo Li, Yanhui Hu, Jia Yu Koh, John D. Eicher, Sylvane Desrivières, Alejandro Arias Vásquez, Ganesh Chauhan, Lavinia Athanasiu, Miguel E. Rentería, Sung Eun Kim, D. Höhn, Nicola J. Armstrong, Qiang Chen, Avram J. Holmes, Anouk den Braber, Iwona Kłoszewska, Micael Andersson, Thomas Espeseth, O. Grimm, Lucija Abramovic, Saud Alhusaini, Yuri Milaneschi, Martina Papmeyer, Tomas Axelsson, Stefan Ehrlich, Roberto Roiz‐Santiáñez, Bernd Kraemer, Asta K. Håberg, Hannah Jones, G. Bruce Pike, Dan J. Stein, Allison Stevens, Janita Bralten, Meike W. Vernooij, Tamara B. Harris, Irina Filippi, A. Veronica Witte, Tulio Guadalupe, Katharina Wittfeld, Thomas H. Mosley, James T. Becker, Nhat Trung Doan, Saskia P. Hagenaars, Yasaman Saba, Gabriel Cuéllar-Partida, Najaf Amin, Saima Hilal, Kwangsik Nho, Nazanin Karbalai, Konstantinos Arfanakis, Diane M. Becker, David Ames, Aaron L. Goldman, Phil H. Lee, Dorret I. Boomsma, Simon Lovestone, Sudheer Giddaluru, Stéphanie Le Hellard, Manuel Mattheisen, Marc M. Bohlken, Dalia Kasperavičiūtė, Lianne Schmaal, Stephen M. Lawrie, Ingrid Agartz, Esther Walton, Diana Tordesillas‐Gutiérrez, Gareth E. Davies, Jean Shin, Jonathan Ipser, Louis Vinke, Martine Hoogman, Maria J. Knol, Tianye Jia, Ralph Burkhardt, Marieke Klein, Fabrice Crivello, Deborah Janowitz, Owen Carmichael, Unn K. Haukvik, Benjamin S. Aribisala, Helena Schmidt, Lachlan T. Strike, Ching‐Yu Cheng, Shannon L. Risacher, Benno Pütz, Debra Fleischman, Amelia A. Assareh, Venkata S. Mattay, Randy L. Buckner, Patrizia Mecocci, Anders M. Dale, Sven Cichon, Marco P. Boks, Mar Matarín, Brenda W.J.H. Penninx, M. Mallar Chakravarty, André F. Marquand, Christine Macare, Shahrzad Kharabian Masouleh, Jaap Oosterlaan, Philippe Amouyel, Katrin Hegenscheid, Jerome I. Rotter, Andrew J. Schork, David C. Liewald, Greig I. de Zubicaray, Tien Yin Wong, Li Shen, Philipp G. Sämann, Henry Brodaty, Joshua L. Roffman, Eco J. C. de Geus, Magda Tsolaki, Susanne Erk, Kristel R. van Eijk, Gianpiero L. Cavalleri, Nic JA van der Wee, Andrew M. McIntosh, Randy L. Gollub, Kazima Bulayeva, Manon Bernard, Jennifer S. Richards, Jayandra J. Himali, Markus Loeffler, Nanda Rommelse, Wolfgang Hoffmann, Lars T. Westlye, Maria C. Valdés Hernández, Narelle K. Hansell, Theo G.M. van Erp, Christiane Wolf, John B. Kwok, Bruno Vellas, Andreas Heinz, Loes M. Olde Loohuis, Norman Delanty, Beng‐Choon Ho, Christopher R. K. Ching, Elena Shumskaya, Albert Hofman, Dennis van der Meer, Georg Homuth, Bruce M. Psaty, Mark E. Bastin, Grant W. Montgomery, Tatiana Foroud, Simone Reppermund, Jouke‐Jan Hottenga, Andrew Simmons, Andreas Meyer‐Lindenberg, Wiepke Cahn, Christopher D. Whelan, Marjolein MJ Van Donkelaar, Qiong Yang, Norbert Hosten, Robert C. Green, Anbupalam Thalamuthu, Sebastian Mohnke, Hilleke E. Hulshoff Pol, Honghuang Lin, Clifford R. Jack, Peter R. Schofield, Thomas W. Mühleisen, Pauline Maillard, Steven G. Potkin, Wei Wen, Evan Fletcher, Arthur W. Toga, Oliver Gruber, Matthew J. Huentelman, George Davey Smith, Lenore J. Launer, Lars Nyberg, Erik G. Jönsson, Benedicto Crespo‐Facorro, Nastassja Koen, Douglas N. Greve, André G. Uitterlinden, Daniel R. Weinberger, Vidar M. Steen, Iryna O. Fedko, Nynke A. Groenewold, Wiro J. Niessen, Roberto Toro, Christophe Tzourio, W.T. Longstreth, M. Kamran Ikram, Jordan W. Smoller, Marie‐José van Tol, Jessika E. Sussmann, Tomáš Paus, Hervé Lemaître, Bernard Mazoyer, Ole A. Andreassen, Dick J. Veltman, Jessica A. Turner, Zdenka Pausová, Günter Schumann, Daan van Rooij, Srdjan Djurovic, Ian J. Deary, Katie L. McMahon, Bertram Müller‐Myhsok, Rachel M. Brouwer, Hilkka Soininen, Massimo Pandolfo, Thomas H. Wassink, Joshua W. Cheung, Thomas Wolfers, Jean‐Luc Martinot, Marcel P. Zwiers, Matthias Nauck, Ingrid Melle, Nicholas G. Martin, Ryota Kanai, Eric Westman, René S. Kahn, Sanjay M. Sisodiya, Tonya White, Arvin Saremi, Hans van Bokhoven, Han G. Brunner, Henry Völzke, Margaret J. Wright, Dennis van ‘t Ent, Markus M. Nöthen, Roel A. Ophoff, Jan K. Buitelaar, Guillén Fernández, Perminder S. Sachdev, Marcella Rietschel, Neeltje EM van Haren, Simon E. Fisher, Alexa Beiser, Clyde Francks, Andrew J. Saykin, Karen A. Mather, Nina Romanczuk‐Seiferth, Catharina A. Hartman, Anita L. DeStefano, Dirk J. Heslenfeld, Michael W. Weiner, Henrik Walter, Pieter J. Hoekstra, Paul Nyquist, Barbara Franke, David A. Bennett, Hans J. Grabe, Andrew D. Johnson, Christopher Chen, Cornelia M. van Duijn, Oscar L. Lopez, Myriam Fornage, Joanna A Wardlaw, Reinhold Schmidt, Charles DeCarli, Philip L. De Jager, Arno Villringer, Stéphanie Debette, Vilmundur Guðnason, Sarah E. Medland, Joshua Shulman, Paul M. Thompson, Sudha Seshadri, M. Arfan Ikram

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2017
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsMontreal Neurological Institute and Hospital
FundersMedical Research Council
KeywordsNeurosciencePutamenBiologyGenetic architectureNucleus accumbensThalamusPhenotypeGlobus pallidusCandidate geneGeneGenome-wide association studyBrainstemGeneticsBasal gangliaSingle-nucleotide polymorphismCentral nervous system

Abstract

fetched live from OpenAlex

Abstract Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.628
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
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

Citations20
Published2017
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenetics and Neurodevelopmental DisordersFrench-language works237,207