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

Hong Yang; Jie Song; Aole Li; Linshuoshuo Lv; Xiaohui Sun; Yingying Mao; Ding Ye

doi:10.3389/fimmu.2023.1139799

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

Front Immunol. 2023 Mar 10:14:1139799. doi: 10.3389/fimmu.2023.1139799. eCollection 2023.

Authors

Hong Yang¹, Jie Song¹, Aole Li², Linshuoshuo Lv¹, Xiaohui Sun¹, Yingying Mao¹, Ding Ye¹

Affiliations

¹ Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China.
² The Fourth College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

Abstract

Background: Evidence from observational studies on the association of folate and vitamin B₁₂ with autoimmune diseases are conflicting.

Objective: We aimed to investigate the relationship of folate and vitamin B₁₂ with autoimmune diseases using Mendelian randomization (MR).

Materials and methods: We selected single-nucleotide polymorphisms associated with folate and vitamin B₁₂ 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.

Results: 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; P = 1.33 × 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 B₁₂ 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.

Conclusion: 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 B₁₂ and risk of IBD.

Keywords: Mendelian randomization; autoimmune diseases; folate; single nucleotide polymorphism; vitamin B12.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoimmune Diseases* / genetics
Folic Acid
Genome-Wide Association Study
Humans
Inflammatory Bowel Diseases* / genetics
Mendelian Randomization Analysis
Vitamin B 12
Vitamins
Vitiligo*

Substances

Vitamin B 12
Folic Acid
Vitamins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82204843, 81973663 and 82174208), the Natural Science Foundation of Zhejiang Province (LQ21H260001 and LQ20H260008), the Foundation of Zhejiang Chinese Medical University (2020ZG01 and 2020ZG16), and the Research Project of Zhejiang Chinese Medical University (2021JKZKTS004A).