Clinical, cosmetic and investigational dermatology · 2025
A Bidirectional Two-Sample Mendelian Randomization Study of Genetic Causality Between Vitamin D Levels and Pemphigus.
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Wang Yanchun, Cheng Shiping, Que Huafa
Аннотация
BACKGROUND: 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.
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.