GBA Mutations in REM Sleep Behavior Disorder and Parkinson’s Disease (S19.007)
Bibliographic record
Abstract
OBJECTIVE: We examined whether GBA mutations are associated with REM sleep Behavior Disorder (RBD) and RBD-associated Parkinson disease (PD). BACKGROUND: RBD patients may progress to PD, Lewy body dementia (LBD) or multiple system atrophy (MSA). RBD patients with PD have increased risk for dementia, autonomic dysfunction and faster progression of PD. Similarly, GBA mutations are also associated with PD, LBD and MSA, and GBA-associated PD patients are also more likely to develop dementia, autonomic dysfunction and faster progression of PD. METHODS: The GBA gene was sequenced in PD (n=525), RBD (n=265) and controls (n=691) of French-Canadian/French origin. Data from European controls with GBA sequencing (n=2240) was collected. RBD screening was performed in 120 Ashkenazi-Jewish PD patients who were previously genotype for founder GBA mutations. Data from the GBA locus was extracted from genome-wide association study of 522 PD patients, 350 RBD patients and 897 controls of French-Canadian/French origin (including the patients and controls that were sequenced for the GBA gene). RESULTS: GBA mutations were found in 10.2[percnt] of RBD, 4.6[percnt] of PD and 1.3[percnt] among our in-house controls and 1.8[percnt] in published European ancestry controls (p<0.001 for all comparisons). GBA-associated PD patients had higher rates of positive screening for probable RBD compared to PD patients without GBA mutations (47[percnt] vs. 24[percnt], p=0.026). In the GBA locus, the strongest marker among RBD patients, rs2230288 (p=1x10-5), was stronger than the marker among PD patient, rs35777901, (p=3x10-4), compared to healthy controls. CONCLUSIONS: GBA mutations and variants are more strongly associated with RBD and with RBD-associated PD, than with PD patients without RBD or sporadic PD. These results suggest that early screening of GBA mutation carriers for RBD may be useful for early identification of individuals who will eventually develop a synucleinopathy. Study Supported by the Michael J. Fox Foundation.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.003 | 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".