Genetically Predicted Serum 25-Hydroxyvitamin D Concentrations in Related to Type 2 Diabetes Mellitus: A Mendelian Randomization Study

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism Pub Date : 2025-07-09 DOI:10.1002/edm2.70050

Jin Yang

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Abstract

Background

In several observational studies, vitamins B6, B9, B12, C and 25-hydroxyvitamin D[25(OH)D] concentrations were associated with type 2 diabetes mellitus (T2DM). Although vitamins play a role in the development of type 2 diabetes mellitus (T2DM), their associations remain unclear.

Objective

This study employed Mendelian randomisation (MR) to explore the causal relationships between circulating concentrations of vitamins B6, B9, B12, C, 25-hydroxyvitamin D and T2DM.

Methods

Single-nucleotide polymorphisms (SNPs) linked to vitamin B6, vitamin B9, vitamin B12, vitamin C and 25(OH)D levels were used as instrumental variables (IVs) in this study. We have two outcomes related to T2DM derived from two genome-wide association studies (GWAS). The first study, referenced by PMID: 3417140, encompasses a cohort of 406,831 individuals of European descent. The second study, identified by PMID: 29892013, includes a sample size of 468,298 Europeans.

Results

Both univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses demonstrate that genetically predicted elevated levels of serum 25(OH)D are consistently associated with a reduced risk of T2DM. In the UVMR analyses, A 1-SD increase in genetically predicted serum 25(OH)D levels, the inverse-variance weighted (IVW) p = 3.8 × 10⁻⁷, p_fdr = 7.6 × 10⁻⁷, the odds ratio(OR) of T2DM (GCST90013942) was 0.67, 95% confidence interval (CI): 0.57–0.78. Furthermore, a 1-SD increase in genetically predicted serum 25(OH)D levels was associated with an OR of 0.987 for T2DM (GCST90029024), the IVW p = 1.1 × 10⁻⁴, p_fdr = 1.1 × 10⁻⁴ with a 95% CI of 0.981–0.994. In the MVMR analyses, genetically predicted higher serum 25(OH)D levels were associated with a decreased risk of T2DM by the IVW p = 1.2 × 10⁻⁵, p_fdr = 5.9 × 10⁻⁵ in GCST90013942 and IVW p = 4.9 × 10⁻⁴, p_fdr = 2.5 × 10⁻³ in GCST90029024. In contrast, levels of vitamins B6, B9, B12, and C did not domenstrate a significant association with T2DM.

Conclusion

Our research reveals that higher circulating serum 25(OH)D levels reduce the possibility of T2DM.

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基因预测血清25-羟基维生素D浓度与2型糖尿病相关：一项孟德尔随机研究

在一些观察性研究中，维生素B6、B9、B12、C和25-羟基维生素D[25(OH)D]浓度与2型糖尿病（T2DM）有关。尽管维生素在2型糖尿病（T2DM）的发展中起作用，但它们之间的关系尚不清楚。目的本研究采用孟德尔随机化方法探讨维生素B6、B9、B12、C、25-羟基维生素D循环浓度与T2DM的因果关系。方法采用与维生素B6、维生素B9、维生素B12、维生素C和25(OH)D水平相关的单核苷酸多态性（snp）作为工具变量（IVs）。我们从两个全基因组关联研究（GWAS）中得到了两个与T2DM相关的结果。第一项研究由PMID: 3417140引用，包括406831名欧洲血统的人。第二项研究由PMID: 29892013确定，包括468,298名欧洲人的样本量。结果单变量孟德尔随机化（UVMR）和多变量孟德尔随机化（MVMR）分析均表明，基因预测的血清25(OH)D水平升高与T2DM风险降低一致相关。在UVMR分析中，遗传预测血清25(OH)D水平增加1-SD，反方差加权（IVW） p = 3.8 × 10−7,pfdr = 7.6 × 10−7,T2DM （GCST90013942）的优势比（OR）为0.67,95%可信区间（CI）： 0.57-0.78。此外，基因预测血清25(OH)D水平升高1 sd与T2DM （GCST90029024）的OR为0.987相关，IVW p = 1.1 × 10−4,pfdr = 1.1 × 10−4,95% CI为0.981-0.994。在MVMR分析中，基因预测较高的血清25(OH)D水平与T2DM风险降低相关，在GCST90013942中IVW p = 1.2 × 10−5,pfdr = 5.9 × 10−5，在GCST90029024中IVW p = 4.9 × 10−4,pfdr = 2.5 × 10−3。相比之下，维生素B6、B9、B12和C的水平与2型糖尿病没有明显的联系。结论本研究表明，较高的循环血清25(OH)D水平可降低T2DM的可能性。

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