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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1811155425569013760 |
---|---|
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. |
first_indexed | 2024-04-10T04:33:48Z |
format | Article |
id | doaj.art-5bdb3e91881e43528ac2308fe4ed6be9 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-10T04:33:48Z |
publishDate | 2023-03-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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 |
work_keys_str_mv | AT hongyang geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT jiesong geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT aoleli geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT linshuoshuolv geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT xiaohuisun geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT yingyingmao geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy AT dingye geneticallypredictedlevelsoffolatevitaminb12andriskofautoimmunediseasesamendelianrandomizationstudy |