Abstract
Genetic and environmental factors jointly affect the onset of multiple sclerosis (MS), among which diet holds considerable interest as a potentially modifiable factor. A nested case-control study was conducted, including 303 participants with MS and 1212 age- and sex-matched controls from the UK Biobank. Conditional logistic regression models were used to estimate the relationship between diet and MS. Mendelian randomization (MR) analysis was employed to examine the genetic associations between various food types and the risk of MS. Mediation analyses were performed to determine the possible mediating effect of serum measurements using the Karlson-Holm-Breen method. Participants who regularly consumed oily fish and consumed more bread per week had a decreased risk of MS. Increased consumption of oily fish and cereal was genetically associated with a lower risk of MS. The association between oily fish intake and reduced risk of MS remained robust among several subgroups. Besides, vitamin D and neutrophil count mediated the protective effects of oily fish consumption against MS, independently. Increasing the intake of both oily fish and wholemeal/wholegrain bread may reduce the risk of MS onset, while vitamin D and neutrophil count play a partial mediating role during this process.