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Record W4407567885 · doi:10.1212/nxg.0000000000200241

Whole Genome Variable Number Tandem Repeat Analysis in Alzheimer Disease

2025· article· en· W4407567885 on OpenAlex
Alesha Heath, M. Windy McNerney, Jerome A. Yesavage

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

VenueNeurology Genetics · 2025
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsnot available
FundersNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteNational Institutes of HealthKarl-Franzens-Universität GrazÖsterreichische ForschungsförderungsgesellschaftNational Institute on AgingMedizinische Universität GrazOesterreichische NationalbankCase Western Reserve UniversityUniversity of TorontoErasmus Medisch CentrumAustrian Science FundZonMwEuropean CommissionEU Joint Programme – Neurodegenerative Disease ResearchRussian Foundation for Basic ResearchNational Institute on Deafness and Other Communication DisordersUniversity of MiamiNational Human Genome Research InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekVanderbilt University
KeywordsVariable number tandem repeatTandem repeatDiseaseGenomeGeneticsBiologyComputational biologyTandemMedicineGenePathologyGenotype

Abstract

fetched live from OpenAlex

Background and Objectives: Investigation into different allelic variants may yield new associative genes to predict late-onset Alzheimer disease (LOAD). Variable number tandem repeats (VNTRs) are important polymorphic components of the genome; however, they have been previously overlooked because of their complex genotyping. New software can now determine differing lengths of VNTRs; however, this has not been tested in a large case-control population. Methods: We used VNTRseek to genotype over 200,000 tandem repeats in 9,501 cases and controls from the Alzheimer's Disease Sequencing Project. We first identified limiting factors of this analysis and then examined the association of VNTRs with AD diagnosis in a subset of non-Hispanic White participants. Results: We found that VNTRs were highly associated with areas of the genome with a high number of previously identified variants. From our case-control analysis, we identified 9 VNTRs with a repeat allele length associated with LOAD including VNTRs on DSC3, NR2E3, CCNY, PKP4, GRAP, and MAP6. Discussion: We were able to show the feasibility of this new type of analysis in large-scale whole-genome sequencing data and identify promising VNTRs that are associated with LOAD.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.220
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.022
GPT teacher head0.285
Teacher spread0.263 · 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