Multiple sclerosis severity variant in DYSF-ZNF638 locus associates with neuronal loss and inflammation
Bibliographic record
Abstract
The genetic variant rs10191329 AA has been identified to associate with faster disability accrual in multiple sclerosis (MS). We investigated the impact of rs10191329 AA carriership on MS pathology and flanking genes dysferlin ( DYSF ) and zinc finger protein 638 ( ZNF638 ) in the Netherlands Brain Bank cohort ( n = 290) by comparing rs10191329 AA ( n = 6) to matched rs10191329 CC carriers ( n = 12). rs10191329 AA carriership associated with more acute axonal stress, reduced layer 2 neuronal density, and a higher proportion of lesions with foamy microglia. In rs10191329 AA donors, normal appearing white matter was characterized by a higher proportion of ZNF638 + oligodendrocytes, and normal appearing gray matter showed more DYSF + cells. Nuclear RNA sequencing showed an upregulation of mitochondrial genes in rs10191329 AA carriers. These data suggest that MS severity associates with an increased susceptibility to neurodegeneration and chronic inflammation. Understanding the role of DYSF, ZNF638, and mitochondrial pathways may reveal new therapeutic targets to attenuate MS progression.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".