Objectives: We conducted a systematic review and wide-angled Mendelian randomization (MR) study to examine the association between possible risk factors and multiple sclerosis (MS).
Methods: We 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.
Results: Childhood 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.
Conclusions: This study identified several modifiable risk factors for primary prevention of MS that should inform public health policy.
Keywords: Mendelian randomization; Multiple sclerosis; Prevention strategy; Risk factors.