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Record W4225246326 · doi:10.1002/alz.12686

Genetic variants in the <i>SHISA6</i> gene are associated with delayed cognitive impairment in two family datasets

2022· article· en· W4225246326 on OpenAlexaff
Jairo Ramos, Laura J. Caywood, Michael B. Prough, Jason E. Clouse, Sharlene D. Herington, Susan H. Slifer, M. Denise Fuzzell, Sarada L. Fuzzell, Sherri D. Hochstetler, Kristy Miskimen, Leighanne R. Main, Michael D. Osterman, Andrew Zaman, Patrice L. Whitehead, Larry D. Adams, Reneé A. Laux, Yeunjoo E. Song, Tatiana Foroud, Richard Mayeux, Peter St George‐Hyslop, Paula Ogrocki, Alan J. Lerner, Jeffery M. Vance, Michael L. Cuccaro, Jonathan L. Haines, Margaret A. Pericak‐Vance, William K. Scott

Bibliographic record

VenueAlzheimer s & Dementia · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHuman-Animal Interaction Studies
Canadian institutionsUniversity of Toronto
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingLeonard M. Miller School of MedicineNational Institutes of HealthCase Western Reserve UniversityMichael J. Fox Foundation for Parkinson's ResearchUniversity of MiamiU.S. Department of Veterans AffairsU.S. Department of Defense
KeywordsHazard ratioDiseaseAlleleSingle-nucleotide polymorphismGenetic associationGeneGeneticsChromosomeBiologyGenome-wide association studyCognitive impairmentCognitionProportional hazards modelMedicineInternal medicineGenotypeNeuroscienceConfidence interval

Abstract

fetched live from OpenAlex

INTRODUCTION: Studies of cognitive impairment (CI) in Amish communities have identified sibships containing CI and cognitively unimpaired (CU) individuals. We hypothesize that CU individuals may carry protective alleles delaying age at onset (AAO) of CI. METHODS: A total of 1522 individuals screened for CI were genotyped. The outcome studied was AAO for CI individuals or age at last normal exam for CU individuals. Cox mixed-effects models examined association between age and single nucleotide variants (SNVs). RESULTS: ) with AAO on chromosomes 6 (rs14538074; hazard ratio [HR] = 3.35), 9 (rs534551495; HR = 2.82), and 17 (rs146729640; HR = 6.38). The chromosome 17 association was replicated in the independent National Institute on Aging Genetics Initiative for Late-Onset Alzheimer's Disease dataset. DISCUSSION: The replicated genome-wide significant association with AAO on chromosome 17 is located in the SHISA6 gene, which is involved in post-synaptic transmission in the hippocampus and is a biologically plausible candidate gene for 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 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 score0.503
Threshold uncertainty score0.629

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 head0.024
GPT teacher head0.316
Teacher spread0.291 · 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 teacher head, 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

Citations7
Published2022
Admission routes1
Has abstractyes

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