Investigating the genetic relationship between vitamin B12 deficiency and Parkinson’s disease
Bibliographic record
Abstract
Abstract Introduction Epidemiological studies suggest that patients with Parkinson’s disease (PD) may have lower levels of vitamin B12 compared to healthy controls, and it was proposed that PD patients could benefit from vitamin B12 supplementation. Functional studies have shown that B12 could modify LRRK2 activity and may directly interact with alpha-synuclein. This study aimed to investigate the role of common and rare variants in genes related to B12 metabolism and assess the potential causal relationships between B12 levels and PD risk, age-at-onset, and motor/cognitive progression. Methods We investigated the association between common and rare variants in genes involved in vitamin B12 metabolism. Rare variants (minor allele frequency < 0.01) were analyzed using the optimal sequence kernel association test (SKAT-O) in 4,815 PD patients and 65,607 controls from two independent cohorts. We constructed pathway-specific polygenic risk scores (PRS) for genes essential to B12 metabolism and for genes identified in previous genome-wide association studies (GWAS) on B12 metabolism. Mendelian randomization and genetic correlation analyses were applied to explore the relationship between vitamin B12 levels and PD risk, age-at-onset, and disease progression. Results Our analysis showed no associations between common variants of genes crucial in B12 metabolism and PD. Pathway PRS identified nominal association between B12-related genes and PD (OR = 1.061, 95% CI: 1.004–1.121, p = 0.038), which did not survive Bonferroni correction. In the rare variants analysis, we identified a significant association between variants with high CADD scores in the CUBN gene (P=6.07E-05; Pfdr=0.005) in the AMP-PD cohort, driven by the benign variant p.G3114S (OR=3.3; p=3.56E-05); however, this was not validated in the meta-analysis. We did not identify a potentially causal relationship between vitamin B12 levels and the risk, age-at-onset, or progression of PD. Additionally, no genetic correlation was observed between vitamin B12 and PD risk or age-at-onset GWASs. Conclusion Overall, our analyses indicate lack of genetic link between B12 levels or metabolism and PD.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".