Circulating Vitamin D Levels and Risk of Vitiligo: Evidence From Meta-Analysis and Two-Sample Mendelian Randomization.

Background: The association between circulating vitamin D levels and risk of vitiligo was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we aimed to evaluate the effect of vitamin D on the risk of vitiigo using meta-analysis and Mendelian randomization (MR). Methods: At the meta-analysis stage, literature search was performed in PubMed and Web of Science to identify eligible observational studies examining the association of circulating 25-hydroxyvitamin D [25(OH)D] or 25-hydroxyvitamin D3 [25(OH)D3] levels with risk of vitiligo up to April 30, 2021. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) of 25(OH)D and 25(OH)D3 in patients with vitiligo relative to controls were pooled. Then at the MR stage, genetic instruments for circulating 25(OH)D (N = 120,618) and 25(OH)D3 (N = 40,562) levels were selected from a meta-analysis of genome-wide association studies (GWAS) of European descent, and summary statistics of vitiligo were obtained from a meta-analysis of three GWASs including 4,680 cases and 39,586 controls. We used inverse-variance weighted (IVW) as main method, followed by weighted-median and likelihood-based methods. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Results: In the meta-analysis, patients with vitiligo had a lower level of circulating 25(OH)D compared with controls [SMD = -1.40; 95% confidence interval (CI): -1.91, -0.89; P < 0.001], while no statistically significant difference of 25(OH)D3 between vitiligo cases and controls was found (SMD = -0.63; 95% CI: -1.29, 0.04; P = 0.064). However, in the MR analyses, genetically predicted 25(OH)D [odds ratio (OR) = 0.93, 95% CI = 0.66-1.31, P = 0.66] and 25(OH)D3 levels (OR = 0.95, 95% CI = 0.80-1.14, P = 0.60) had null associations with risk of vitiligo using the IVW method. Sensitivity analyses using alternative MR methods and instrumental variables (IV) sets obtained consistent results, and no evidence of pleiotropy or outliers was observed. Conclusion: Our study provided no convincing evidence for a causal effect of 25(OH)D or 25(OH)D3 levels on the risk of vitiligo. Further longitudinal and experimental studies, as well as functional studies are warranted to elucidate the role of vitamin D in the development of vitiligo.

Song J ，Liu K ，Chen W ，Liu B ，Yang H ，Lv L ，Sun X ，Mao Y ，Ye D ... -  《Frontiers in Nutrition》

Causal association of genetically determined circulating vitamin D metabolites and calcium with multiple sclerosis in participants of European descent.

Vitamin D is an important regulator of calcium. Mendelian randomization (MR) studies exclusively focused on the circulating total 25-hydroxyvitamin D (25(OH)D) as a biomarker of vitamin D status, and have found the causal association between 25(OH)D and the risk of multiple sclerosis (MS). However, it currently remains unclear about the causal association of the 25(OH)D subtypes including 25(OH)D3 and C3-epi-25(OH)D3, as well as calcium with the risk of MS. We performed a two-sample MR study to evaluate the causal association of circulating total 25(OH)D, 25(OH)D3, C3-epi-25(OH)D3, and calcium with the risk of MS using large-scale genome-wide association studies (GWAS) datasets from total 25(OH)D (n = 417,580), 25(OH)D3 (n = 40,562), C3-epi-25(OH)D3 (n = 40,562), calcium (n = 305,349), and MS (14,802 MS and 26,703 controls). We selected five MR methods including inverse-variance weighted (IVW), simple median, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier), and contamination mixture method. IVW showed that the genetically increased circulating 25(OH)D level (OR = 0.81, 95% CI: 0.70-0.94, P = 4.00E-03), circulating 25(OH)D3 level (OR = 0.85, 95% CI: 0.76-0.95, P = 5.00E-03), and circulating C3-epi-25(OH)D3 level (OR = 0.85, 95% CI: 0.74-0.98, P = 2.30E-02) were causally associated with reduced risk of MS. However, IVW showed no causal association between circulating calcium level and the risk of MS with OR = 2.85, 95% CI: 0.42-19.53, P = 2.85E-01. Our current findings together with evidence from other MR studies support the use of vitamin D but not calcium supplementation for the prevention of MS.

Zhang Y ，Liu H ，Zhang H ，Han Z ，Wang T ，Wang L ，Liu G ... -  《-》

[Associations between vitamin D levels and systemic lupus erythematosus risk:a Mendelian randomized study].

Ren YQ ，Liu JP ，Cui Y 《-》

Causal Associations between Vitamin D Levels and Psoriasis, Atopic Dermatitis, and Vitiligo: A Bidirectional Two-Sample Mendelian Randomization Analysis.

Ren Y ，Liu J ，Li W ，Zheng H ，Dai H ，Qiu G ，Yu D ，Yao D ，Yin X ... -  《Nutrients》

Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study.

The coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial. We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. We found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility [IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197-0.9988, p = 0.0473], severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699-1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819-1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy. Our MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

Cui Z ，Tian Y 《Journal of Translational Medicine》