BMI and low vitamin D are causal factors for multiple sclerosis: A Mendelian Randomization study.
Level 3 - non-randomized controlled study
Two-sample Mendelian randomization study using consortium GWAS summary statistics
PubMed 31937597 · doi:10.1212/NXI.0000000000000662
What was done
The authors performed a two-sample Mendelian randomization analysis using GWAS summary statistics from relevant consortia to evaluate causal estimates of adult BMI, childhood BMI, and vitamin D status on multiple sclerosis (MS) risk. Primary analyses used random-effects inverse-variance-weighted meta-analysis, accompanied by sensitivity and multivariable analyses.
What was found
Genetically determined childhood BMI (OR 1.24, 95% CI 1.05–1.45, p = 0.011) and adult BMI (OR 1.14, 95% CI 1.01–1.30, p = 0.042) were associated with increased MS risk. When excluding 16 childhood-BMI-associated variants, the effect of adult BMI lost statistical significance (OR 1.11, 95% CI 0.97–1.28, p = 0.121). Multivariate adjustment for vitamin D did not alter these associations. Each genetically determined unit increase in log-transformed vitamin D was associated with lower MS odds (OR 0.57, 95% CI 0.41–0.81, p = 0.001).
Why it matters
This study provides evidence that childhood adiposity prior to age 10 is an independent risk factor for MS, clarifying that earlier life BMI may drive the link between obesity and MS, while reinforcing vitamin D as a protective factor.
Limits
The abstract does not report participant counts, GWAS cohort demographics, ancestral diversity, or specific pleiotropy test results.
Cited by
- supports Vitamin D deficiency increases the risk of developing multiple sclerosis.