The relative contributions of obesity, vitamin D, leptin and adiponectin to multiple sclerosis risk: a Mendelian randomization mediation analysis

Adil Harroud, Despoina Manousaki, Guillaume Butler-Laporte, Ruth E Mitchell, George Davey Smith, J Brent Richards, Sergio E Baranzini

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Downloads (Pure)

Abstract

Background:
Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear.

Objective:
To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS.

Methods:
We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators.

Results:
Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09–1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60–0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%–31.0%).

Conclusions:
This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.
Original languageEnglish
Number of pages7
JournalMultiple Sclerosis Journal
Early online date19 Feb 2021
DOIs
Publication statusE-pub ahead of print - 19 Feb 2021

Keywords

  • multiple sclerosis
  • Mendelian randomization
  • obesity
  • vitamin D
  • genetic epidemiology

Fingerprint Dive into the research topics of 'The relative contributions of obesity, vitamin D, leptin and adiponectin to multiple sclerosis risk: a Mendelian randomization mediation analysis'. Together they form a unique fingerprint.

Cite this