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 《-》

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

Zheng JS ，Luan J ，Sofianopoulou E ，Sharp SJ ，Day FR ，Imamura F ，Gundersen TE ，Lotta LA ，Sluijs I ，Stewart ID ，Shah RL ，van der Schouw YT ，Wheeler E ，Ardanaz E ，Boeing H ，Dorronsoro M ，Dahm CC ，Dimou N ，El-Fatouhi D ，Franks PW ，Fagherazzi G ，Grioni S ，Huerta JM ，Heath AK ，Hansen L ，Jenab M ，Jakszyn P ，Kaaks R ，Kühn T ，Khaw KT ，Laouali N ，Masala G ，Nilsson PM ，Overvad K ，Olsen A ，Panico S ，Quirós JR ，Rolandsson O ，Rodríguez-Barranco M ，Sacerdote C ，Spijkerman AMW ，Tong TYN ，Tumino R ，Tsilidis KK ，Danesh J ，Riboli E ，Butterworth AS ，Langenberg C ，Forouhi NG ，Wareham NJ ... -  《-》

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》

Association between circulating 25-hydroxyvitamin D metabolites and periodontitis: Results from the NHANES 2009-2012 and Mendelian randomization study.

This study sought to investigate associations of 25-hydroxyvitamin D (25(OH)D) metabolites with periodontitis and to assess causality using Mendelian randomization (MR). This study included 7246 participants of the National Health and Nutrition Examination Survey, 2009-2012. The association of periodontitis with 25(OH)D metabolites was assessed using multivariable logistic regression analysis. Two-sample MR for 25(OH)D, 25(OH)D3 , and C3-epi-25(OH)D3 with periodontitis (n = 17,353 cases/28,210 controls) was conducted. The principal analysis employed the inverse-variance-weighted (IVW) approach. We controlled for horizontal pleiotropy using five additional methods. Based on the observational study, each 1-point increase in standard deviation of 25(OH)D lowered the risk of periodontitis by 15% (OR = 0.85, 95% confidence interval [CI]: 0.78-0.93, p = .006) after multivariable adjustment. A similar relationship was observed between 25(OH)D3 and periodontitis (OR = 0.88, 95% CI: 0.80-0.97, p = .031). Furthermore, a potential non-linear association was found between periodontitis and both 25(OH)D and 25(OH)D3 . However, C3-epi-25(OH)D3 was not found to be associated with periodontitis risk. IVW-MR showed that periodontitis risk was not significantly associated with genetically increased levels of 25(OH)D (OR = 1.02, 95% CI: 0.90-1.16, p = .732), 25(OH)D3 (OR = 1.04, 95% CI: 0.93-1.17, p = .472), or C3-epi-25(OH)D3 (OR = 1.11, 95% CI: 0.87-1.41, p = .400). The pleiotropy-robust MR approaches yielded similar results after we had eliminated the variants with horizontal pleiotropy risk. Cross-sectional observational analysis identified significant relationships between periodontitis with 25(OH)D metabolites, while findings based on MR study did not support a causal role.

Li W ，Zheng Q ，Xu M ，Zeng C ，Deng X ... -  《-》