The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis
Bibliographic record
Abstract
BACKGROUND: Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear. OBJECTIVE: To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS. METHODS: We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators. RESULTS: Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09-1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60-0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%-31.0%). CONCLUSIONS: This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.
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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 | 0.003 | 0.034 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".