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Record W2964750218 · doi:10.1038/s42003-019-0537-9

A genome-wide association study identifies genetic loci associated with specific lobar brain volumes

2019· article· en· W2964750218 on OpenAlexaff
Sven J. van der Lee, Maria J. Knol, Ganesh Chauhan, Claudia L. Satizábal, Albert V. Smith, Edith Hofer, Joshua C. Bis, Derrek P. Hibar, Saima Hilal, Erik B. van den Akker, Konstantinos Arfanakis, Manon Bernard, Lisa R. Yanek, Najaf Amin, Fabrice Crivello, Josh W. Cheung, Tamara B. Harris, Yasaman Saba, Oscar L. Lopez, Shuo Li, Jeroen van der Grond, Lei Yu, Tomáš Paus, Gennady V. Roshchupkin, Philippe Amouyel, Neda Jahanshad, Kent D. Taylor, Qiong Yang, Rasika A. Mathias, Stefan Böehringer, Bernard Mazoyer, Kenneth Rice, Ching‐Yu Cheng, Pauline Maillard, Tien Yin Wong, Wiro J. Niessen, Alexa Beiser, Marian Beekman, Wanting Zhao, Paul Nyquist, Christopher Chen, L. J. Launer, Bruce M. Psaty, Muhammad Ikram, Meike W. Vernooij, Helena Schmidt, Zdenka Pausová, Diane M. Becker, Philip L. De Jager, Paul M. Thompson, Cornelia M. van Duijn, David A. Bennett, P. Eline Slagboom, Reinhold Schmidt, W.T. Longstreth, M. Arfan Ikram, Sudha Seshadri, Stéphanie Debette, Vilmundur Guðnason, Hieab H.H. Adams, Charles DeCarli

Bibliographic record

VenueCommunications Biology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsHolland Bloorview Kids Rehabilitation HospitalSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersNational Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNational Institute on AgingAgence Nationale de la RechercheAlzheimer's Disease Neuroimaging Initiative
KeywordsBrain sizeOccipital lobeGenome-wide association studyBiologyParietal lobeTemporal lobeNeuroscienceFrontal lobeGenetic associationGeneticsSingle-nucleotide polymorphismGeneMedicineGenotypeEpilepsyMagnetic resonance imaging

Abstract

fetched live from OpenAlex

Abstract Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications ( DAAM1 and THBS3 ), or close to genes causing Mendelian brain-related diseases ( ZIC4 and FGFRL1 ). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.052
Threshold uncertainty score0.942

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.000
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 head0.019
GPT teacher head0.272
Teacher spread0.254 · 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.

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

Citations36
Published2019
Admission routes1
Has abstractyes

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