Brain morphology mediating the effects of common genetic risk variants on Alzheimer’s disease
Bibliographic record
Abstract
Background: Late-onset Alzheimer's disease (LOAD) has been associated with alterations in the morphology of multiple brain structures, and it is likely that disease mechanisms differ between brain regions. Coupling genetic determinants of LOAD with measures of brain morphology could localize and identify primary causal neurobiological pathways. Objective: To determine causal pathways from genetic risk variants of LOAD via brain morphology to LOAD. Methods: Mediation and Mendelian randomization (MR) analysis were performed using common genetic variation, T1 MRI and clinical data collected by UK Biobank and Alzheimer's Disease Neuroimaging Initiative. Results: ε4 on LOAD. MR showed that a thinner entorhinal cortex, a smaller hippocampus and amygdala, and a larger volume of the inferior lateral ventricles, increased the risk of LOAD as well as vice versa. Conclusions: Combining neuroimaging and genetic data can give insight into the causal neuropathological pathways of LOAD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".