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Record W4393044051 · doi:10.1002/alz.13705

Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data

2024· article· en· W4393044051 on OpenAlexaff
Yanbing Wang, Chloé Sarnowski, Honghuang Lin, Achilleas Pitsillides, Nancy L. Heard‐Costa, Seung Hoan Choi, Dongyu Wang, Joshua C. Bis, Elizabeth Blue, Eric Boerwinkle, Philip L. De Jager, Myriam Fornage, Ellen M. Wijsman, Sudha Seshadri, Josée Dupuis, Gina M. Peloso, Anita L. DeStefano

Bibliographic record

VenueAlzheimer s & Dementia · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill University
FundersNational Institute on AgingUniversity of Pennsylvania
KeywordsGenome-wide association studyWhole genome sequencingBiologyGeneticsGenetic associationGenomeGene1000 Genomes ProjectComputational biologyDNA sequencingGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

INTRODUCTION: Genome-wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci. METHODS: We performed single common variant association analysis and rare variant aggregate analyses in the pooled population (N cases = 2184, N controls = 2383) and targeted analyses in subpopulations using WGS data from the Alzheimer's Disease Sequencing Project (ADSP). The analyses were restricted to variants within 100 kb of 83 previously identified GWAS lead variants. RESULTS: Seventeen variants were significantly associated with AD within five genomic regions implicating the genes OARD1/NFYA/TREML1, JAZF1, FERMT2, and SLC24A4. KAT8 was implicated by both single variant and rare variant aggregate analyses. DISCUSSION: This study demonstrates the utility of leveraging WGS to gain insights into AD loci identified via GWAS.

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)0.003
metaresearch head score (Gemma)0.005
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: none
Teacher disagreement score0.012
Threshold uncertainty score0.039

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.006
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0120.006

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 head0.070
GPT teacher head0.319
Teacher spread0.249 · 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

Citations22
Published2024
Admission routes1
Has abstractyes

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