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Record W2749059461 · doi:10.1016/j.celrep.2017.11.028

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

2017· article· en· W2749059461 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueCell Reports · 2017
Typearticle
Languageen
FieldMedicine
TopicChemokine receptors and signaling
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Center for Research ResourcesNational Institute of Dental and Craniofacial ResearchNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteTrinity College, University of OxfordBiotechnology and Biological Sciences Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilCanadian Institutes of Health ResearchUniversity of California, Los AngelesNational Institutes of HealthNational Institute on AgingCentre for Cognitive Ageing and Cognitive EpidemiologyNovo Nordisk FondenNational Institute on Alcohol Abuse and AlcoholismUniversity of EdinburghUniversitetet i BergenAcademy of FinlandBergens ForskningsstiftelseTrinity College DublinHelse VestMinistry of EducationNorges ForskningsrådNational Institute on Drug AbuseNovo NordiskUniversity of MinnesotaStiftelsen Kristian Gerhard JebsenNational Science FoundationScience Foundation IrelandJohns Hopkins UniversityFolkhälsanin TutkimussäätiöDirectorate for Biological SciencesGlaxoSmithKlineEllison Medical FoundationCentre for Addiction and Mental Health FoundationCedars-Sinai Medical CenterHelsingin YliopistoFinska LäkaresällskapetEmil Aaltosen SäätiöBoston University
KeywordsGenome-wide association studyComputational biologyNeuroscienceNootropicDrug discoveryBiologyDrugCognitionBioinformaticsComputer sciencePharmacologyGeneticsGene

Abstract

fetched live from OpenAlex

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

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.

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 categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.074
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.029
GPT teacher head0.289
Teacher spread0.260 · 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