Polygenic scores for disease risk are not associated with clinical outcomes in Parkinson’s disease
Bibliographic record
Abstract
Polygenic risk scores (PRS) in Parkinson's disease (PD) are associated with disease risk. Recently, pathway-specific PRS have been created to take advantage of annotations inking variants to biological pathways or cell types. Here, we investigated 8 biological pathways or regions of open chromatin using pathway-specific PRS: alpha-synuclein pathway, adaptive immunity, innate immunity, lysosomal pathway1, endocytic membrane-trafficking pathway, mitochondrial pathway, microglial open chromatin single nucleotide polymorphisms (SNPs), and monocyte open chromatin SNPs. We analysed 7,402 PD patients across 18 'in-person' PD cohorts, and 6,717 patients from the online Fox Insight study. We did not find any significant associations between the 8 pathway-specific PRSs and 8 clinical outcomes in PD. Though this may be due to a lack of statistical power and limited sample size, it may also suggest that the genetic architecture of sporadic PD risk is different from the genetics of PD progression and clinical outcomes.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".