Abstract
ObjectivesWe conducted a systematic review and wide-angled Mendelian randomization (MR) study to examine the association between possible risk factors and multiple sclerosis (MS).MethodsWe used MR analysis to assess the associations between 65 possible risk factors and MS using data from a genome-wide association study including 14 498 cases and 24 091 controls of European ancestry. For 18 exposures not suitable for MR analysis, we conducted a systematic review to obtain the latest meta-analyses evidence on their associations with MS.ResultsChildhood and adulthood body mass index were positively associated with MS, whereas physical activity and serum 25-hydroxyvitamin D were inversely associated with MS. There was evidence of possible associations of type 2 diabetes, waist circumference, body fat percentage, age of puberty and high-density lipoprotein cholesterol. Data of systematic review showed that exposure to organic solvents, Epstein Barr virus and cytomegalovirus virus infection, and diphtheria and tetanus vaccination were associated with MS risk.ConclusionsThis study identified several modifiable risk factors for primary prevention of MS that should inform public health policy.
Highlights
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and a leading nontraumatic cause of disability among young adults of northernElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.European ancestry [1]
Liability to type 2 diabetes, childhood and adulthood body mass index, waist circumference and body fat percentage were positively associated with MS risk, whereas age of puberty was inversely associated with risk
Using Mendelian randomization (MR) analysis, we found that 4 out of 65 risk factors were robustly associated with MS risk, including childhood and adulthood body mass index, serum 25-hydroxyvitamin D and physical activity
Summary
Even though epidemiological studies have uncovered several modifiable risk factors for MS, such as serum vitamin D levels [2] and body mass index [3], the overall etiological basis of MS is poorly understood [4]. A recent umbrella review found consistent evidence supporting the associations of Epstein-Barr virus infection and smoking with MS risk [1]. The role of other environmental factors and internal conditions for MS risk have been scarcely investigated. It is unclear whether the associations reported by traditional observational studies are causal due to potential confounding, reverse causality and misclassification of such studies
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