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 B12 with autoimmune diseases are conflicting.ObjectiveWe aimed to investigate the relationship of folate and vitamin B12 with autoimmune diseases using Mendelian randomization (MR).Materials and methodsWe selected...

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Main Authors: Hong Yang, Jie Song, Aole Li, Linshuoshuo Lv, Xiaohui Sun, Yingying Mao, Ding Ye
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139799/full
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author Hong Yang
Jie Song
Aole Li
Linshuoshuo Lv
Xiaohui Sun
Yingying Mao
Ding Ye
author_facet Hong Yang
Jie Song
Aole Li
Linshuoshuo Lv
Xiaohui Sun
Yingying Mao
Ding Ye
author_sort Hong Yang
collection DOAJ
description BackgroundEvidence from observational studies on the association of folate and vitamin B12 with autoimmune diseases are conflicting.ObjectiveWe aimed to investigate the relationship of folate and vitamin B12 with autoimmune diseases using Mendelian randomization (MR).Materials and methodsWe 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.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 × 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.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 B12 and risk of IBD.
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spelling doaj.art-5bdb3e91881e43528ac2308fe4ed6be92023-03-10T05:16:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11397991139799Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization studyHong Yang0Jie Song1Aole Li2Linshuoshuo Lv3Xiaohui Sun4Yingying Mao5Ding Ye6Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Fourth College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaBackgroundEvidence from observational studies on the association of folate and vitamin B12 with autoimmune diseases are conflicting.ObjectiveWe aimed to investigate the relationship of folate and vitamin B12 with autoimmune diseases using Mendelian randomization (MR).Materials and methodsWe 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.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 × 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.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 B12 and risk of IBD.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139799/fullfolatevitamin B12autoimmune diseasesMendelian randomizationsingle nucleotide polymorphism
spellingShingle Hong Yang
Jie Song
Aole Li
Linshuoshuo Lv
Xiaohui Sun
Yingying Mao
Ding Ye
Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
Frontiers in Immunology
folate
vitamin B12
autoimmune diseases
Mendelian randomization
single nucleotide polymorphism
title Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
title_full Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
title_fullStr Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
title_full_unstemmed Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
title_short Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study
title_sort genetically predicted levels of folate vitamin b12 and risk of autoimmune diseases a mendelian randomization study
topic folate
vitamin B12
autoimmune diseases
Mendelian randomization
single nucleotide polymorphism
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139799/full
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