Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS

Neurology. 2017 Apr 25;88(17):1623-1629. doi: 10.1212/WNL.0000000000003849. Epub 2017 Mar 29.

Abstract

Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS).

Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10,875 controls) and Sweden (n = 175 cases, 5,376 controls; total n = 16,820).

Results: Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01, and over 100 non-human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model.

Conclusions: We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS.

Publication types

  • Meta-Analysis
  • Multicenter Study

MeSH terms

  • Adolescent
  • Age of Onset
  • Biomarkers / blood
  • Body Mass Index*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease*
  • HLA-DRB1 Chains / genetics
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism*
  • Risk
  • Sweden
  • United States
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • Biomarkers
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • Vitamin D
  • 25-hydroxyvitamin D