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Record W4401834444 · doi:10.1101/2024.08.13.24311922

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

2024· preprint· en· W4401834444 on OpenAlexaff
Luis M. García‐Marín, Adrián I. Campos, Santiago Díaz‐Torres, Jill A. Rabinowitz, Zuriel Ceja, Brittany L. Mitchell, Katrina L. Grasby, Jackson G. Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole A. Andreassen, Konstantinos Arfanakis, Alejandro Arias Vásquez, Nicola J. Armstrong, Lavinia Athanasiu, Mark E. Bastin, Alexa Beiser, David A. Bennett, Marco P. Boks, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Jan K. Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince D. Calhoun, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Sven Cichon, Benedicto Crespo‐Facorro, Fabrice Crivello, Anders M. Dale, George Davey Smith, Eco J. C. de Geus, Philip L. De Jager, Greig I. de Zubicaray, Stéphanie Debette, Charles DeCarli, Chantal Depondt, Sylvane Desrivières, Srdjan Djurovic, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Guillén Fernández, Irina Filippi, Simon E. Fisher, Debra Fleischman, Evan Fletcher, Myriam Fornage, Andreas J. Forstner, Clyde Francks, Barbara Franke, Tian Ge, Aaron L. Goldman, Hans J. Grabe, Robert C. Green, O. Grimm, Nynke A. Groenewold, Oliver Gruber, Vilmundur Guðnason, Asta K. Håberg, Unn K. Haukvik, Andreas Heinz, Derrek P. Hibar, Saima Hilal, Jayandra J. Himali, Beng‐Choon Ho, David Hoehn, Pieter J. Hoekstra, Edith Hofer, Wolfgang Hoffmann, Avram J. Holmes, Georg Homuth, Norbert Hosten, M. Kamran Ikram, Jonathan Ipser, Clifford R. Jack, Neda Jahanshad, Erik G. Jönsson, René S. Kahn, Ryota Kanai, Marieke Klein, Maria J. Knol, Lenore J. Launer, Stephen M. Lawrie, Stéphanie Le Hellard, Phil H. Lee, Hervé Lemaître, Shuo Li, David C. Liewald, Honghuang Lin, W. T. Longstreth, Oscar L. López, Michelle Luciano, Pauline Maillard, André F. Marquand, Nicholas G. Martin, Jean-Luc Martinot, Karen A. Mather, Venkata S. Mattay, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer‐Lindenberg, Nazanin Mirza‐Schreiber, Yuri Milaneschi, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller‐Myhsok, Susana Muñoz Maniega, Matthias Nauck, Kwangsik Nho, Wiro J. Niessen, Markus M. Nöthen, Paul Nyquist, Jaap Oosterlaan, Massimo Pandolfo, Tomáš Paus, Zdenka Pausová, Brenda W.J.H. Penninx, G. Bruce Pike, Bruce M. Psaty, Benno Pütz, Simone Reppermund, Marcella Rietschel, Shannon L. Risacher, Nina Romanczuk‐Seiferth, Rafael Romero-Garcia, Gennady V. Roshchupkin, Jerome I. Rotter, Perminder S. Sachdev, Philipp G. Sämann, Arvin Saremi, Muralidharan Sargurupremraj, Andrew J. Saykin, Lianne Schmaal, Helena Schmidt, Reinhold Schmidt, Peter R. Schofield, Markus Scholz, Günter Schumann, Emanuel Schwarz, Li Shen, Jean Shin, Sanjay M. Sisodiya, Albert V. Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, Dan J. Stein, Jason L. Stein, Sophia I. Thomopoulos, Arthur W. Toga, Diana Tordesillas‐Gutiérrez, Julian N. Trollor, María Valdés Hernández, Dennis van ‘t Ent, Hans van Bokhoven, Dennis van der Meer, Nic JA van der Wee, Javier Vázquez-Bourgón, Dick J. Veltman, Meike W. Vernooij, Arno Villringer, Louis Vinke, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Lars T. Westlye, Eric Westman, Tonya White, A. Veronica Witte, Christiane Wolf, Jingyun Yang, Marcel P. Zwiers, M. Arfan Ikram, Sudha Seshadri, Paul M. Thompson, Claudia L. Satizábal, Sarah E. Medland, Miguel E. Rentería

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsHospital for Sick ChildrenSickKids FoundationUniversity of TorontoUniversité de MontréalCentre Hospitalier Universitaire Sainte-JustineUniversity of CalgaryMcGill University
Fundersnot available
KeywordsPutamenNeuroscienceThalamusNucleus accumbensGlobus pallidusBiologyCaudate nucleusGenome-wide association studyAmygdalaBrain sizeHippocampusVentral tegmental areaPsychologyBasal gangliaGeneGeneticsMedicineSingle-nucleotide polymorphismCentral nervous systemDopaminergicGenotypeDopamine

Abstract

fetched live from OpenAlex

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signalling and brain ageing-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and ADHD. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

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 machine prediction

Teacher imitation

Not 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)0.004
metaresearch head score (Gemma)0.008
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 score0.006
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0020.004
Science and technology studies0.0000.001
Scholarly communication0.0020.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.016
GPT teacher head0.303
Teacher spread0.287 · 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 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

Citations0
Published2024
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicGenetic Associations and Epidemiology→French-language works237,207→