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Record W2010192073 · doi:10.1371/journal.pone.0079771

Alzheimer’s Disease: Analyzing the Missing Heritability

2013· article· en· W2010192073 on OpenAlexfundno aff
Perry G. Ridge, Shubhabrata Mukherjee, Paul K. Crane, John Kauwe

Bibliographic record

VenuePLoS ONE · 2013
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersNational Institute of Neurological Disorders and StrokeNational Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthMedical Research CouncilHersenstichtingUniversitat de BarcelonaBristol-Myers SquibbNorth Bristol NHS TrustHoward Hughes Medical InstituteEisaiNational Cancer InstituteStichting MS ResearchEli Lilly and CompanyAlzheimer's Research TrustNorthern California Institute for Research and EducationMedpaceNational Center for Research ResourcesF. Hoffmann-La RocheWellcome TrustBrigham Young UniversityGlaxoSmithKlinePfizerNovartisElanNewcastle UniversityOffice of Research and DevelopmentU.S. Department of Veterans AffairsSynarcDana FoundationAlzheimer's AssociationAstraZeneca
KeywordsInternational HapMap ProjectGenome-wide association studySingle-nucleotide polymorphismBiologyGeneticsHeritabilityGenotypingMissing heritability problemGenetic associationApolipoprotein EDiseaseGenotypePhenotypeMedicineGenePathology

Abstract

fetched live from OpenAlex

Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

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)0.017
metaresearch head score (Gemma)0.061
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 score0.017
Threshold uncertainty score0.092

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0170.061
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.005
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.000

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 head0.094
GPT teacher head0.309
Teacher spread0.215 · 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

Citations344
Published2013
Admission routes1
Has abstractyes

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