BMI, Low Vitamin D Are Independent Causal Risk Factors of MS, Study Finds

Body mass index (BMI) and low vitamin D are causal factors for multiple sclerosis (MS), according to a recent study published in Neurology Neuroimmunology & Neuroinflammation.

Researchers conducted primary analyses of a random-effects inverse-weighted meta-analysis and secondary sensitivity analyses in a 2 sample Mendelian randomization (MR). In MR analyses, “genetic variants associated with a trait are combined to form an instrumental variable which acts as a proxy for the trait; this can then be used to determine causal associations with outcomes of interest,” the authors said.

Specifically, the researchers found “novel evidence that BMI before the age of 10 is an independent causal risk factor for MS.” Their results also strengthened “evidence for the causal role of vitamin D in the pathogenesis od MS.” Several other previously confirmed environmental risk factors for MS include Epstein-Barr virus infection, smoking, and obesity.

Using information from publicly available data sources, the researchers found that increased childhood BMI that is genetically determined (odds ratio [OR_MS], 1.24; 95% CI, 1.05-1.45; P = .011) and adult BMI (OR_MS, 1.14; 95% CI, 1.01-1.30; P = .042) were both associated with a greater risk of MS.

“Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% decrease in the odds of MS (OR, 0.57; 95% CI, 0.41-0.81; P = .001),” the researchers said. They also noted a significant effect of genetically determined MS risk on the status of vitamin D (OR, 0.99; 95% CI, 0.98-1.0; P = .008). This implies MS may reduce vitamin D levels.

In addition, they found there was no evidence of significant pleiotropy in the estimates of risk factors. “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,” they said.

Researchers warn that targeting childhood obesity and low vitamin D on a population level are not effective strategies for MS. However, addressing these risk factors in high-risk individuals (those with a strong family history) early on, “will have a more profound effect," on diagnoses and treatment of the disease.

Reference

Jacobs BM, Noyce AJ, Giovannoni G, Dobson R. BMI and low vitamin D are causal factors for multiple sclerosis: a Mendelian randomization study [printed online January 14, 2020]. Neurol Neuroimmunol Neuroinflamm. doi: 10.1212/NXI.0000000000000662.