Genetically predicted levels of folate, vitamin B₁₂, and risk of autoimmune diseases: A Mendelian randomization study

BackgroundEvidence from observational studies on the association of folate and vitamin B-12 with autoimmune diseases are conflicting. ObjectiveWe aimed to investigate the relationship of folate and vitamin B-12 with autoimmune diseases using Mendelian randomization (MR). Materials and methodsWe selected single-nucleotide polymorphisms associated with folate and vitamin B-12 at the genome-wide significance level. Summary-level data for four common autoimmune diseases (vitiligo, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus) were obtained from large-scale genome-wide association studies, with a sample size of 44,266, 86,640, 58,284, and 23,210, respectively. MR analyses were conducted using the inverse variance weighted (IVW) approach, and sensitivity analyses were further performed to test the robustness. ResultsWe found that a higher genetically determined serum folate level per one standard deviation (SD) was associated with a decreased risk of vitiligo by the IVW method [odds ratios (OR) = 0.47; 95% confidence interval (CI): 0.32-0.69; P = 1.33 x 10(-4)]. Sensitivity analyses using alternative methods showed similar associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.919). In addition, we observed that vitamin B-12 per one SD was positively associated with IBD (IVW: OR = 1.14, 95% CI: 1.03-1.26, P = 0.010; maximum likelihood: OR = 1.14, 95% CI: 1.01-1.29, P = 0.035; MR-PRESSO: OR = 1.14, 95% CI:1.01-1.28, P =0.037), while the association was not significant after Bonferroni correction. ConclusionThe study provides convincing evidence for an inverse association between serum folate level and risk of vitiligo. Further studies are warranted to elucidate the possible association between vitamin B-12 and risk of IBD.