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Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis

OBJECTIVE: The VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization. METHODS: We used data...

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Autores principales: Zhao, Sizheng Steven, Mason, Amy, Gjekmarkaj, Eva, Yanaoka, Haruyuki, Burgess, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614794/
https://www.ncbi.nlm.nih.gov/pubmed/37437450
http://dx.doi.org/10.1016/j.semarthrit.2023.152238
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author Zhao, Sizheng Steven
Mason, Amy
Gjekmarkaj, Eva
Yanaoka, Haruyuki
Burgess, Stephen
author_facet Zhao, Sizheng Steven
Mason, Amy
Gjekmarkaj, Eva
Yanaoka, Haruyuki
Burgess, Stephen
author_sort Zhao, Sizheng Steven
collection PubMed
description OBJECTIVE: The VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization. METHODS: We used data from 332,984 participants of the UK Biobank of whom 23,089 had at least one autoimmune disease defined using ICD code and/or self-report. Diseases were further considered in mechanistic subgroups driven by “autoimmunity” (n=12,774) or “autoinflammation” (n=11,164), then individually. We selected variants within gene regions implicated in vitamin D biology to generate a weighted genetic score. We performed population-wide analysis using the ratio method, then examined non-linear effects across five quantiles based on 25-hydroxycholecalciferol levels. RESULTS: Genetically-predicted vitamin D was associated with lower risk of diseases in the autoinflammation group (OR 0.95 per 10ng/ml increase in 25-hydroxycholecalciferol; 95%CI 0.91-0.99; p=0.03) but not the autoimmunity group (OR 0.99; 95%CI 0.95-1.03; p=0.64) or combined. When considering individual diseases, genetically-predicted vitamin D was associated with lower risk of psoriasis (OR 0.91; 95%CI 0.85-0.97; p=0.005), the most common disease in the autoinflammation group, and suggestively with systemic lupus erythematosus (OR 0.84; 95%CI 0.69-1.02; p=0.08); results were replicated using data from independent studies. We found no evidence for a plausible non-linear relationship between vitamin D and any outcome. CONCLUSIONS: We found genetic evidence to support a causal link between 25-hydroxycholecalciferol concentrations and psoriasis and systemic lupus erythematosus. These results have implications for potential disease prevention strategies, and the interpretation and design of vitamin D supplementation trials.
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spelling pubmed-76147942023-07-21 Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis Zhao, Sizheng Steven Mason, Amy Gjekmarkaj, Eva Yanaoka, Haruyuki Burgess, Stephen Semin Arthritis Rheum Article OBJECTIVE: The VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization. METHODS: We used data from 332,984 participants of the UK Biobank of whom 23,089 had at least one autoimmune disease defined using ICD code and/or self-report. Diseases were further considered in mechanistic subgroups driven by “autoimmunity” (n=12,774) or “autoinflammation” (n=11,164), then individually. We selected variants within gene regions implicated in vitamin D biology to generate a weighted genetic score. We performed population-wide analysis using the ratio method, then examined non-linear effects across five quantiles based on 25-hydroxycholecalciferol levels. RESULTS: Genetically-predicted vitamin D was associated with lower risk of diseases in the autoinflammation group (OR 0.95 per 10ng/ml increase in 25-hydroxycholecalciferol; 95%CI 0.91-0.99; p=0.03) but not the autoimmunity group (OR 0.99; 95%CI 0.95-1.03; p=0.64) or combined. When considering individual diseases, genetically-predicted vitamin D was associated with lower risk of psoriasis (OR 0.91; 95%CI 0.85-0.97; p=0.005), the most common disease in the autoinflammation group, and suggestively with systemic lupus erythematosus (OR 0.84; 95%CI 0.69-1.02; p=0.08); results were replicated using data from independent studies. We found no evidence for a plausible non-linear relationship between vitamin D and any outcome. CONCLUSIONS: We found genetic evidence to support a causal link between 25-hydroxycholecalciferol concentrations and psoriasis and systemic lupus erythematosus. These results have implications for potential disease prevention strategies, and the interpretation and design of vitamin D supplementation trials. 2023-06-30 2023-06-30 /pmc/articles/PMC7614794/ /pubmed/37437450 http://dx.doi.org/10.1016/j.semarthrit.2023.152238 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license. https://creativecommons.org/licenses/by/4.0/For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission https://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhao, Sizheng Steven
Mason, Amy
Gjekmarkaj, Eva
Yanaoka, Haruyuki
Burgess, Stephen
Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title_full Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title_fullStr Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title_full_unstemmed Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title_short Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
title_sort associations between vitamin d and autoimmune diseases: mendelian randomization analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614794/
https://www.ncbi.nlm.nih.gov/pubmed/37437450
http://dx.doi.org/10.1016/j.semarthrit.2023.152238
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