Investigating causal associations between pork intake and multiple sclerosis using Mendelian randomization: Insights from large-scale GWAS data in European populations

Background Observational studies propose associations between dietary factors and multiple sclerosis (MS). However, the causal nature of these relationships remains unclear. This study aims to determine whether nutritional factors causally influence MS risk through Mendelian randomization (MR) analysis. Methods Summary statistics for 15 common dietary factors were derived from the Genome-Wide Association Study (GWAS) conducted by the Medical Research Council Integrated Epidemiology Unit (MRC-IEU). The GWAS data of MS were sourced from the International Multiple Sclerosis Genetics Consortium (IMSGC), including 14,498 cases and 24,091 controls. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach to estimate causality, while Cochran's Q test assessed heterogeneity. MR-Egger (MRE) and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were employed to detect pleiotropy and conduct sensitivity analyses. Results We executed univariable- and multivariable-adjusted MR analyses, incorporating adjustments for past tobacco smoking, particulate matter air pollution (PM2.5) and moderate to vigorous physical activity. The univariable Mendelian randomization (UVMR) analysis elucidated potential causal relationships concerning the risk of MS for only two dietary factors: pork intake (odds ratio [OR] = 6.764, 95% confidence interval [CI]: 1.772–25.814, p = 0.005 by IVW) and fish/liver oil dietary supplements (OR = 0.119, 95%CI: 0.032–0.444, p = 0.002 by IVW). In the multivariate Mendelian randomization (MVMR) analysis, the significant causal relationship between pork intake and MS remained robust even after adjusting for potential confounders. Conversely, after adjusting for these confounders, the initially observed causal associations between fish/liver oil dietary supplements and MS ceased to be statistically significant. Conclusions Our findings suggest that pork intake could increase the risk of MS. Other nutritional factors analyzed in this study did not exhibit significant correlations with MS.