Associations Between Dietary Factors, Metabolic Factors, Sleep Disorders, Physical Activity, and the Risk of Multiple Sclerosis: A Univariable and Multivariable Mendelian Randomization Study

Observational studies propose associations between sleep disorders, dietary factors, metabolic factors, physical activity, and multiple sclerosis (MS). However, the causal nature of these relationships remains unclear. This study aims to determine whether these factors causally influence MS risk through Mendelian randomization (MR) analysis. We utilized two‐sample MR to investigate the causal relationships between 29 distinct traits related to sleep disorders, dietary factors, metabolic factors, physical activity, and their impact on MS. The inverse‐variance weighted (IVW) method served as the primary analytical tool to estimate causality. Univariate Mendelian randomization analyses (UVMR) demonstrated that higher genetically predicted chronotype (OR = 0.571; p = 0.044), pork intake (OR = 6.764; p = 0.005), fish/liver oil dietary supplements (OR = 0.119, p = 0.002), body mass index (BMI, OR = 1.347; p = 0.004), type 2 diabetes (T2DM, OR = 1.122; p = 0.032), hip circumference (OR = 1.267; p = 0.023), short sleep duration (OR = 0.170; p = 0.013), and moderate to vigorous physical activity (MVPA, OR = 0.282; p < 0.001) were significantly associated with the risk of MS. In the multivariate Mendelian randomization (MVMR) analyses, the significant causal associations between pork intake, BMI, T2DM, and MVPA with MS were robust even after adjusting for potential confounding variables. However, after adjusting for these confounders, the initially observed causal links between the remaining four exposure factors and MS were no longer statistically significant. This study suggests that certain factors may have a causal relationship with MS risk. Specifically, increased participation in moderate to vigorous physical activity may reduce the risk of MS, whereas higher BMI, greater pork intake, and a history of T2DM may increase the risk of MS.