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Genetic variants for head size share genes and pathways with cancer
Maria J. Knol, Raymond A. Poot, Tavia E. Evans, Claudia L. Satizábal, Aniket Mishra, Muralidharan Sargurupremraj, Sandra Van der Auwera, Marie‐Gabrielle Duperron, Xueqiu Jian, Dianne H.K. van Dam-Nolen, Sander Lamballais, Mikołaj A. Pawlak, Cora E. Lewis, Amaia Carrión-Castillo, Theo G.M. van Erp, Céline S. Reinbold, Jean Shin, Markus Scholz, Asta K. Håberg, Anders Kämpe, Gloria Hoi‐Yee Li, Reut Avinun, Joshua Atkins, Fang‐Chi Hsu, Alyssa R. Amod, Max Lam, Ami Tsuchida, Mariël W.A. Teunissen, Nil Aygün, Yash Patel, Dan Liang, Alexa Beiser, Frauke Beyer, Joshua C. Bis, Daniël Bos, R. Nick Bryan, Robin Bülow, Svenja Caspers, Gwénaëlle Catheline, Charlotte A. M. Cecil, Shareefa Dalvie, Jean‐François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M. Ford, Barbara Franke, Barry I. Freedman, Nele Friedrich, Melissa J. Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M. Kamran Ikram, Clifford R. Jack, Neda Jahanshad, Christiane Jockwitz, Shuo Li, Keane Lim, W. T. Longstreth, Fabìo Macciardi, Philippe Amouyel, Konstantinos Arfanakis, Benjamin S. Aribisala, Mark E. Bastin, Ganesh Chauhan, Christopher Chen, Ching‐Yu Cheng, Philip L. De Jager, Ian J. Deary, Debra Fleischman, Rebecca F. Gottesman, Vilmundur Guðnason, Saima Hilal, Edith Hofer, Deborah Janowitz, J. Wouter Jukema, David C. Liewald, Lorna M. Lopez, Oscar L. López, Michelle Luciano, Oliver Martinez, Wiro J. Niessen, Paul Nyquist, Jerome I. Rotter, Tatjana Rundek, Ralph L. Sacco, Helena Schmidt, Henning Tiemeier, Stella Trompet, Jeroen van der Grond, Henry Völzke, Joanna M. Wardlaw, Lisa R. Yanek, Jingyun Yang, Ingrid Agartz, Saud Alhusaini, Laura Almasy, David Ames, Katrin Amunts, Ole A. Andreassen, Nicola J. Armstrong, Manon Bernard, John Blangero, Laura M. E. Blanken, Marco P. Boks, Dorret I. Boomsma, Adam M. Brickman, Henry Brodaty, Randy L. Buckner, Jan K. Buitelaar, Dara M. Cannon, Vaughan J. Carr, Stanley V. Catts, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Aiden Corvin, Benedicto Crespo‐Facorro, Joanne E. Curran, Gareth E. Davies, Eco J. C. de Geus, Greig I. de Zubicaray, Anouk den Braber, Sylvane Desrivières, Allissa Dillman, Srdjan Djurovic, Wayne C. Drevets, Ravi Duggirala, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Simon E. Fisher, Tatiana Foroud, Tian Ge, Sudheer Giddaluru, David C. Glahn, Aaron L. Goldman, Robert C. Green, Corina U. Greven, O. Grimm, Narelle K. Hansell, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Frans Henskens, Derrek P. Hibar, Beng‐Choon Ho, Pieter J. Hoekstra, Avram J. Holmes, Martine Hoogman, Jouke‐Jan Hottenga, Hilleke E. Hulshoff Pol, Assen Jablensky, Mark Jenkinson, Tianye Jia, Karl-Heinz Jöckel, Erik G. Jönsson, Sungeun Kim, Marieke Klein, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Stéphanie Le Hellard, Hervé Lemaître, Carmel M. Loughland, André F. Marquand, Nicholas G. Martin, Jean-Luc Martinot, Mar Matarín, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Colm McDonald, Francis J. McMahon, Katie L. McMahon, E Rebekah, McWhirter, Patrizia Mecocci, Ingrid Melle, Andreas Meyer‐Lindenberg, Patricia T. Michie, Yuri Milaneschi, Derek W. Morris, Bryan Mowry, Kwangsik Nho, Thomas E. Nichols, Rene L. Olvera, Jaap Oosterlaan, Roel A. Ophoff, Massimo Pandolfo, Christos Pantelis, Irene Pappa, Brenda W.J.H. Penninx, G. Bruce Pike, Paul E. Rasser, Miguel E. Rentería, Simone Reppermund, Marcella Rietschel, Shannon L. Risacher, Nina Romanczuk‐Seiferth, Emma J. Rose, Perminder S. Sachdev, Philipp G. Sämann, Andrew J. Saykin, Ulrich Schall, Peter R. Schofield, Sara Schramm, Günter Schumann, Rodney J. Scott, Li Shen, Sanjay M. Sisodiya, Hilkka Soininen, Emma Sprooten, Velandai Srikanth, Vidar M. Steen, Lachlan T. Strike, Anbupalam Thalamuthu, Arthur W. Toga, Paul A. Tooney, Diana Tordesillas‐Gutiérrez, Jessica A. Turner, María Valdés Hernández, Dennis van der Meer, Nic J.A. van der Wee, Neeltje E. M. van Haren, Dennis van ‘t Ent, Dick J. Veltman, Henrik Walter, Daniel R. Weinberger, Michael Weiner, Wei Wen, Lars T. Westlye, Eric Westman, Anderson M. Winkler, Girma Woldehawariat, Margaret J. Wright, Jing Wu, Outi Mäkitie, Bernard Mazoyer, Sarah E. Medland, Susumu Miyamoto, Susanne Moebus, Thomas H. Mosley, Ryan L. Muetzel, Thomas W. Mühleisen, Manabu Nagata, Soichiro Nakahara, Zdenka Pausová, Adrian Preda, Yann Quidé, William R. Reay, Gennady V. Roshchupkin, Reinhold Schmidt, Pamela J. Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beaté St Pourcain, Jason L. Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad van der Lugt, Meike W. Vernooij, David J. Werring, B. Gwen Windham, A. Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G. Brunner, Quentin Le Grand, Kang Sim, Dan J. Stein, Donald W. Bowden, Murray J. Cairns, Ahmad R. Hariri, Ching‐Lung Cheung, Sture Andersson, Arno Villringer, Tomáš Paus, Sven Cichon, Vince D. Calhoun, Fabrice Crivello, Lenore J. Launer, Tonya White, Peter J. Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J. Grabe, M. Arfan Ikram, Stéphanie Debette, Paul M. Thompson, Sudha Seshadri, Hieab H.H. Adams
Bibliographic record
VenueCell Reports Medicine · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsUniversité de MontréalMcGill UniversityCentre Hospitalier Universitaire Sainte-JustineUniversity of TorontoSickKids FoundationHospital for Sick Children
FundersNational Center for Advancing Translational SciencesNational Institute of Neurological Disorders and StrokeNational Center for Research ResourcesNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute on Drug AbuseNational Institute of Mental HealthNational Institute on AgingJapan Society for the Promotion of ScienceMinisterie van Onderwijs, Cultuur en WetenschapNational Health and Medical Research CouncilSiemens HealthineersMedical Research CouncilCanadian Institutes of Health ResearchWake Forest School of MedicineUniversity of AlabamaMacquarie Group FoundationAgence Nationale de la RechercheUniversität GreifswaldNational Institutes of HealthHeinz Nixdorf StiftungRamsay Health CareUniversity College London Hospitals NHS Foundation TrustSanofiFondation de FranceNational Heart, Lung, and Blood InstituteKaiser Foundation Research InstituteUniversity of MinnesotaVetenskapsrådetNovo NordiskErasmus Medisch CentrumAustralian Schizophrenia Research BankBritish Heart FoundationMinistry of Education, Culture, Sports, Science and TechnologyBundesministerium für Bildung und ForschungZonMwNederlandse Organisatie voor Wetenschappelijk OnderzoekInstitut National de la Santé et de la Recherche MédicaleGovernment of OntarioNational Institute for Health and Care ResearchPratt FoundationUniversité de BordeauxCompute CanadaFondation Bettencourt SchuellerWellcome TrustUniversity of Alabama at BirminghamUniversity of TorontoU.S. Department of Veterans AffairsEuropean CommissionSchool of Medicine, Boston UniversityHeart and Stroke Foundation of CanadaStroke AssociationNorthwestern UniversitySuomen Lääketieteen SäätiöEU Joint Programme – Neurodegenerative Disease ResearchBundesministerium für Wissenschaft, Forschung und WirtschaftU.S. Department of Health and Human Services
KeywordsBiologyGeneWnt signaling pathwayBrain sizeGeneticsHuman genomeGenomeHuman brainNeuroscienceMedicine
Abstract
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
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 imitationNot 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 categoriesnone
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 score0.729
Threshold uncertainty score0.357
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 head0.013
GPT teacher head0.240
Teacher spread0.228 · 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 teacher head, not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
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
Citations10
Published2024
Admission routes2
Has abstractyes