Genetic Childhood BMI Affects MS Risk

Genetically determined increased body mass index (BMI) before age 10 years is a causal risk factor of multiple sclerosis (MS), independent of vitamin D, according to novel evidence from a new study. 

The study’s findings also strengthen evidence for the causal role of vitamin D in the pathogenesis of MS, according to the researchers.

Previous Mendelian randomization (MR) studies have demonstrated causal relationships between low vitamin D, adult BMI, and MS risk; results for childhood BMI have been conflicting. To develop updated estimates for how BMI and vitamin D status impact MS risk, the researchers used univariate and multivariate MR, which also controlled for confounding.

Summary statistics for single nucleotide polymorphism associations with traits of interest were obtained from the relevant consortia.

The researchers determined that genetically determined increased childhood BMI and adult BMI were associated with increased MS risk. In fact, each genetically determined unit increase in adult BMI was associated with a 14% increase in the odds of MS.

After excluding 16 variants associated with childhood BMI, there was a decreased effect of genetically determined adult BMI on MS risk. 

The direction or significance of these estimates did not change following a correction for effects of serum vitamin D in a multivariate analysis.

“Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% decrease in the odds of MS,” the researchers wrote.

The study authors also highlighted the fact that there was no evidence of significant pleiotropy in the association between childhood BMI and MS risk.

“Although we cannot exclude that this causal effect is mediated through adult BMI, adult BMI is a function of early life BMI, and therefore, we would argue this is a case of vertical, rather than horizontal pleiotropy which does not invalidate the MR assumptions,” the researchers concluded.

—Colleen Murphy

Reference:

Jacobs BM, Noyce AJ, Giovannoni G, Dobson R. BMI and low vitamin D are causal factors for multiple sclerosis: a Mendelian randomization study. Neurol Neuroimmunol Neuroinflamm. 2020;7(2). https://doi.org/10.1212/NXI.0000000000000662.