Low Vitamin D in Obesity Not Associated With Risk for Multiple Sclerosis
Among the environmental factors that have been associated with increased risk for MS are low vitamin D levels and adolescent/young adulthood obesity.
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According to a study presented at the third annual ACTRIMS Forum, held February 1 through 3, 2018 in San Diego, California, obesity-associated lowering of vitamin D levels may not mediate the putative causal relationship between obesity and multiple sclerosis (MS).1
Among the environmental factors that have been associated with increased risk for MS are Epstein-Barr virus infection, exposure to cigarette smoke, low vitamin D levels, and adolescent/young adulthood obesity — the latter association being restricted to women.2 In addition, obesity has been associated with low serum levels of 25-hydroxyvitamin D.
In the current study, the investigators sought to evaluate the causal relationship between obesity and development of adult-onset MS, independent of vitamin D levels. Because of the lack of high-quality data from randomized studies investigating the direct causal inference of obesity on MS, the researchers used Mendelian randomization.
A genome-wide association study (GWAS) by the Genetic Investigation of Anthropometric Traits (GIANT) consortium of body mass index (BMI; n=322,105 of European descent) identified 97 loci associated with BMI.3 Based on these identified genetic variants, the researchers involved in the current study previously determined that genetically elevated BMI affects MS susceptibility (ie, a BMI change from ≥25 kg/m2 [overweight] to ≥30 kg/m2 [obese] during childhood/early adulthood leads to an estimated 4.1% increase in risk for MS).4
In 2017, the International MS Genetics Consortium conducted a GWAS meta-analysis to estimate the effects of these identified loci on MS by their association with BMI.5 The study included data from 14,802 patients with MS and 26, 703 healthy controls. The effects of these BMI-associated loci on vitamin D levels were evaluated in a subsequent study in which GWAS and whole genome sequencing were combined (n=42,274). Estimates from the effects of BMI and vitamin D were used in the current study in which a Mendelian randomization approach was taken to evaluate the vitamin D-adjusted effect of BMI on MS of BMI.
The researchers identified a total of 76 BMI-related variants from the GIANT study and found that 1 standard deviation increase in BMI led to a 34% increased risk for MS (odds ratio [OR] 1.34; 95% CI, 1.10-1.64; P =.003). Adjusting for vitamin D levels did not significantly modify this association (33% risk increase; OR 1.33; 95% CI, 1.09-1.63, P =.005).
“This study demonstrates that the effect of obesity on MS risk is not mediated only by lowered vitamin D levels,” concluded the investigators, adding, “These findings provide motivation to better understand how obesity increases the risk of MS.”
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- Harroud A, Morris, JA, Manousaki D, et al. Distinct effects of obesity and vitamin D on risk of multiple sclerosis: a Mendelian randomization study. Presented at: ACTRIMS Forum 2018; February 1-3, 2018; San Diego, CA. Poster 091.
- Gianfrancesco MA, Barcellos LF. Obesity and multiple sclerosis susceptibility: a review. J Neurol Neuromedicine. 2016;1(7):1-5.
- Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518: 197-206.
- Mokry LE, Ross S, Timpson NJ, Sawcer S, Smith GD, Richards JB. Obesity and multiple sclerosis: A Mendelian randomization study. PLoS Med. 2016; 13: e1002053.
- International Multiple Sclerosis Genetics Consortium. The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility. BioRXiv. doi: 10.1101/143933