Summary
Objectives: We explored whether genetically predicted increased body mass index (BMI) modulates multiple sclerosis (MS) risk through interleukin-6 (IL-6) signaling. Methods: We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets for BMI, IL-6 signaling, IL-6 levels and c-reactive protein (CRP) levels as exposures and estimated their effects on risk of MS from GWAS data from the International Multiple Sclerosis Genetics Consortium (IMSGC) in 14,802 MS cases and 26,703 controls. Results: = 0.046). The proportion of the effect of BMI on MS mediated by IL-6 signaling corresponded to 43% (95% CI = 25%-54%). In contrast to IL-6 signaling, there was little evidence for an effect of serum IL-6 levels or CRP levels on risk of MS.
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