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Record W1643374004 · doi:10.1038/ncomms8549

Large-scale genomics unveil polygenic architecture of human cortical surface area

2015· article· en· W1643374004 on OpenAlexfundno aff
Chi‐Hua Chen, Qian Peng, Andrew J. Schork, Min‐Tzu Lo, Chun-Chieh Fan, Yunpeng Wang, Francesco Bettella, Donald J. Hagler, Connor McCabe, Linda Chang, Natacha Akshoomoff, Erik Newman, Thomas Ernst, Peter C.M. van Zijl, Joshua Kuperman, Sarah Murray, Cinnamon S. Bloss, Mark I. Appelbaum, Anthony Gamst, Wesley K. Thompson, Hauke Bartsch, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Leslie M. Shaw, Zaven S. Khachaturian, Greg Sorensen, María C. Carrillo, Lew Kuller, Marc Raichle, Steven M. Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulman, William Z. Potter, Peter J. Snyder, Adam J. Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matt A. Bernstein, Nick C. Fox, Paul R. Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Virginia M.‐Y. Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Leon J. Thal, Richard Frank, Neil Buckholtz, Marilyn Albert, John Hsiao, Lars T. Westlye, William S. Kremen, Terry L. Jernigan, Stéphanie Le Hellard, Vidar M. Steen, Thomas Espeseth, Matt Huentelman, Asta K. Håberg, Ingrid Agartz, Srdjan Djurovic, Ole A. Andreassen, Nicholas J. Schork, Anders M. Dale

Bibliographic record

VenueNature Communications · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Institute on Drug AbuseNational Institute of Mental HealthNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchUniversity of California, San DiegoNational Institutes of HealthIXICOServierHelse Midt-NorgeNorthern California Institute for Research and EducationEisaiSynarcNorges Teknisk-Naturvitenskapelige UniversitetPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaMedpaceNovartis Pharmaceuticals CorporationNational Alliance for Research on Schizophrenia and DepressionU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeMeso Scale DiagnosticsAlzheimer's AssociationGenentechNorges ForskningsrådFoundation for the National Institutes of Health
KeywordsHeritabilitySingle-nucleotide polymorphismBiologyGenetic architectureGenomicsGenomeEvolutionary biologyGeneticsGenetic variationGeneQuantitative trait locusGenotype

Abstract

fetched live from OpenAlex

Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h(2)∼0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.

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)0.001
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 score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.026
GPT teacher head0.311
Teacher spread0.286 · 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

Citations36
Published2015
Admission routes1
Has abstractyes

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