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Assessment of the genetic variance of late-onset Alzheimer's disease

2016· article· en· W2289147497 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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueNeurobiology of Aging · 2016
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersJanssen Research and DevelopmentNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Institute on AgingGenentechAlzheimer's Drug Discovery FoundationNational Institutes of HealthH. Lundbeck A/SGE HealthcareUniversitat de BarcelonaFujirebio EuropeMedical Research CouncilServierCanadian Institutes of Health ResearchStichting MS ResearchNewcastle UniversityHigher Education Funding Council for EnglandNational Association for Colitis and Crohn's DiseaseNorth Bristol NHS TrustBanner Alzheimer’s FoundationNorthern California Institute for Research and EducationIXICOTakeda Pharmaceutical CompanyBiogenPfizerBioClinicaAlzheimer's Disease Neuroimaging InitiativeBiomedical Laboratory Research and Development, VA Office of Research and DevelopmentU.S. Department of DefenseBRACEF. Hoffmann-La RocheU.S. Department of Veterans AffairsUniversity of PennsylvaniaWellcome TrustEisaiUniversity of Southern CaliforniaHersenstichtingEli Lilly and CompanyBrigham Young UniversityAbbVieUniversity of California, San DiegoOffice of Research and DevelopmentMerckGlaxoSmithKlineNational Center for Advancing Translational SciencesNovartis Pharmaceuticals CorporationWellcomeAlzheimer's AssociationNational Cancer InstituteLundbeckfondenAlzheimer's Research TrustBristol-Myers SquibbHoward Hughes Medical InstituteNational Institute of Biomedical Imaging and BioengineeringNational Human Genome Research InstituteJohnson and JohnsonMeso Scale Diagnostics
KeywordsSingle-nucleotide polymorphismBiologyTREM2Genetic architectureGenetic variationGeneticsGenome-wide association studyPhenotypeGenetic associationExplained variationGenotypeGeneReceptorStatistics

Abstract

fetched live from OpenAlex

Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.212

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 science0.0000.000
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 head0.025
GPT teacher head0.319
Teacher spread0.294 · 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