Neuroanatomical correlates of polygenic risk for Parkinson’s Disease
Bibliographic record
Abstract
Abstract Parkinson ‘s Disease (PD) is heritable, however how genetic risk confers vulnerability remains mostly unknown. Here we use genetic and neuroimaging measures from 20,000 healthy adults from the UK Biobank to show that PD polygenic risk score (PRS) is associated with cortical thinning in a pattern that resembles cortical atrophy seen in PD. Conversely, PD PRS is associated with a global increase in cortical surface area. We also show that the genetically determined cortical thinning profile overlaps with the expression of genes associated with synaptic signaling, is dependent on anatomical connectivity and on regional expression of the most significant PD risk genes. Despite identical PRS distributions in males and females, only males show the associated brain features, possibly explaining the sex disparity in PD. We discuss potential mechanisms linking genetic risk to cortical thickness and surface area, and suggest that the divergent effects may reflect separate routes of genetic vulnerability.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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 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".