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Multiple sclerosis (MS) is a chronic demyelinating disease that is associated with permanent disability and low quality of life. Development of MS is attributed to a combination of genetic and environmental factors. Genome-wide association studies revealed more than 200 variants that are associated with risk of MS. An umbrella review showed that smoking, history of infectious mononucleosis, and anti-Epstein-Barr virus nuclear antigen (anti-EBNA) immunoglobulin G (IgG) seropositivity are credible risk factors of MS. In the present narrative review, we updated our published umbrella review, showing that body mass index in childhood and adolescence and anti-viral capsid antigen (anti-VCA) IgG seropositivity are additional credible risk factors of MS. In addition, we discuss the findings from Mendelian randomization studies, which present evidence for a potential causal role of serum vitamin D and adulthood body mass index on risk of MS. Finally, we discuss the potential limitations of meta-analyses, umbrella reviews, and Mendelian randomization studies in the search for risk factors of MS.

Original publication




Journal article


Mult Scler

Publication Date





397 - 404


Biomarkers, Mendelian randomization, environmental factors, meta-analysis, multiple sclerosis, risk factors, umbrella review, Adolescent, Adult, Antigens, Viral, Body Mass Index, Child, Humans, Infectious Mononucleosis, Mendelian Randomization Analysis, Meta-Analysis as Topic, Multiple Sclerosis, Smoking