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
Bibliographic record
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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".