Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole‐genome sequencing from the Alzheimer's Disease Sequencing Project
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- Meta-epidemiology (narrow)
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.148
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.231 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Abstract INTRODUCTION Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. METHODS We investigated the association of AD with both common variants and aggregates of rare coding and non‐coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. RESULTS Pooled‐population analyses of all individuals identified genetic variants at apolipoprotein E ( APOE ) and BIN1 associated with AD ( p < 5 × 10 −8 ). Subgroup‐specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non‐coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals ( p = 1.9 × 10 −9 ). Finally, we observed rare non‐coding variants in the promoter of TOMM40 distinct of APOE in pooled‐population analyses ( p = 7.2 × 10 −8 ). DISCUSSION We observed that complementary pooled‐population and subgroup‐specific analyses offered unique insights into the genetic architecture of AD. Highlights We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E ( APOE ), BIN1 , PSEN1 , and LINC00320 associated with AD. We observed rare non‐coding variants in the promoter of TOMM40 distinct of APOE .
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.
The record
- Venue
- Alzheimer s & Dementia
- Topic
- Genomics and Rare Diseases
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- McGill University
- Funders
- National Heart, Lung, and Blood InstituteNational Institute on Aging
- Keywords
- PSEN1GeneticsBiologyGenome-wide association studyApolipoprotein EGenetic associationAlzheimer's diseasePopulationGenetic architectureWhole genome sequencingSingle-nucleotide polymorphismDiseaseGenomeGenotypeGenePresenilinMedicineQuantitative trait locusPathology
- Has abstract in OpenAlex
- yes