A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus

Yanchun Wang,1 Shiping Cheng,2 Huafa Que3 1College of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Dermatology, the Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s...

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Main Authors: Wang Y, Cheng S, Que H
Format: Article
Language:English
Published: Dove Medical Press 2025-05-01
Series:Clinical, Cosmetic and Investigational Dermatology
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Online Access:https://www.dovepress.com/a-bidirectional-two-sample-mendelian-randomization-study-of-genetic-ca-peer-reviewed-fulltext-article-CCID
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author Wang Y
Cheng S
Que H
author_facet Wang Y
Cheng S
Que H
author_sort Wang Y
collection DOAJ
description Yanchun Wang,1 Shiping Cheng,2 Huafa Que3 1College of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Dermatology, the Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China; 3Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huafa Que, Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, No. 725 Wanping South Road, Shanghai, 200032, People’s Republic of China, Email huafaque@126.comBackground: Pemphigus, a B-cell-mediated autoimmune disease, has been hypothesized to involve vitamin D due to its immunomodulatory effects on B-cell activity. However, observational studies on this association remain inconclusive due to confounding factors. This study used genome-wide association study (GWAS) data for bidirectional two-sample Mendelian randomization (MR) analysis to clarify causality.Materials and Methods: Genetic instruments for serum vitamin D levels (61 SNPs) and pemphigus (3 SNPs) were analyzed via inverse variance weighting (IVW), weighted median, and MR-Egger regression. Forward MR analysis revealed no causal effect of vitamin Don pemphigus risk [IVW OR=0.835 (95% CI:0.318– 2.189), P=0.623], consistent across sensitivity analyses. Conversely, reverse MR showed pemphigus did not influence vitamin D levels [IVW OR=1.000 (95% CI:0.993– 1.006), P=0.867]. Heterogeneity (Cochran Q test) and pleiotropy (MR-Egger intercept) tests confirmed robustness of results.Results: Our findings challenge the presumed causal link between vitamin D and pemphigus, suggesting observed associations may arise from confounding factors. This underscores the need for mechanistic studies to explore alternative pathways in pemphigus pathogenesis.Keywords: vitamin D, pemphigus, Mendelian randomization analysis, genome-wide association study
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institution Kabale University
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spelling doaj-art-08b1db45e7894e37bb792d65448530aa2025-08-20T03:53:11ZengDove Medical PressClinical, Cosmetic and Investigational Dermatology1178-70152025-05-01Volume 18Issue 111671176102840A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and PemphigusWang Y0Cheng S1Que H2College of Clinical Medicine, Jiangxi University of Chinese MedicineSchool of clinical medicineDepartment of SurgeryYanchun Wang,1 Shiping Cheng,2 Huafa Que3 1College of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Dermatology, the Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China; 3Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huafa Que, Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, No. 725 Wanping South Road, Shanghai, 200032, People’s Republic of China, Email huafaque@126.comBackground: Pemphigus, a B-cell-mediated autoimmune disease, has been hypothesized to involve vitamin D due to its immunomodulatory effects on B-cell activity. However, observational studies on this association remain inconclusive due to confounding factors. This study used genome-wide association study (GWAS) data for bidirectional two-sample Mendelian randomization (MR) analysis to clarify causality.Materials and Methods: Genetic instruments for serum vitamin D levels (61 SNPs) and pemphigus (3 SNPs) were analyzed via inverse variance weighting (IVW), weighted median, and MR-Egger regression. Forward MR analysis revealed no causal effect of vitamin Don pemphigus risk [IVW OR=0.835 (95% CI:0.318– 2.189), P=0.623], consistent across sensitivity analyses. Conversely, reverse MR showed pemphigus did not influence vitamin D levels [IVW OR=1.000 (95% CI:0.993– 1.006), P=0.867]. Heterogeneity (Cochran Q test) and pleiotropy (MR-Egger intercept) tests confirmed robustness of results.Results: Our findings challenge the presumed causal link between vitamin D and pemphigus, suggesting observed associations may arise from confounding factors. This underscores the need for mechanistic studies to explore alternative pathways in pemphigus pathogenesis.Keywords: vitamin D, pemphigus, Mendelian randomization analysis, genome-wide association studyhttps://www.dovepress.com/a-bidirectional-two-sample-mendelian-randomization-study-of-genetic-ca-peer-reviewed-fulltext-article-CCIDVitamin DPemphigusMendelian randomization analysisGenome-wide association study
spellingShingle Wang Y
Cheng S
Que H
A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
Clinical, Cosmetic and Investigational Dermatology
Vitamin D
Pemphigus
Mendelian randomization analysis
Genome-wide association study
title A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
title_full A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
title_fullStr A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
title_full_unstemmed A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
title_short A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus
title_sort bidirectional two sample mendelian randomization study of genetic causality between vitamin d levels and pemphigus
topic Vitamin D
Pemphigus
Mendelian randomization analysis
Genome-wide association study
url https://www.dovepress.com/a-bidirectional-two-sample-mendelian-randomization-study-of-genetic-ca-peer-reviewed-fulltext-article-CCID
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