AUTHOR=Yang Hong , Song Jie , Li Aole , Lv Linshuoshuo , Sun Xiaohui , Mao Yingying , Ye Ding 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1139799

DOI=10.3389/fimmu.2023.1139799

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Evidence from observational studies on the association of folate and vitamin B<sub>12</sub> with autoimmune diseases are conflicting.</p></sec><sec><title>Objective</title><p>We aimed to investigate the relationship of folate and vitamin B<sub>12</sub> with autoimmune diseases using Mendelian randomization (MR).</p></sec><sec><title>Materials and methods</title><p>We selected single-nucleotide polymorphisms associated with folate and vitamin B<sub>12</sub> 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.</p></sec><sec><title>Results</title><p>We 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; <italic>P</italic> = 1.33 × 10<sup>-4</sup>]. Sensitivity analyses using alternative methods showed similar associations, and no evidence of pleiotropy was detected by MR-Egger regression (<italic>P</italic> = 0.919). In addition, we observed that vitamin B<sub>12</sub> per one SD was positively associated with IBD (IVW: OR = 1.14, 95% CI: 1.03–1.26, <italic>P</italic> = 0.010; maximum likelihood: OR = 1.14, 95% CI: 1.01–1.29, <italic>P</italic> = 0.035; MR-PRESSO: OR = 1.14, 95% CI:1.01–1.28, <italic>P</italic> =0.037), while the association was not significant after Bonferroni correction.</p></sec><sec><title>Conclusion</title><p>The 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<sub>12</sub> and risk of IBD.</p></sec>