维生素 D 与 IEU 开放 GWAS 项目中的妊娠糖尿病：两样本双向 Mendelian 随机研究。
Vitamin D and Gestational Diabetes Mellitus in the IEU OpenGWAS Project: A Two-Sample Bidirectional Mendelian Randomization Study.
机构信息
Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China.
出版信息
Nutrients. 2024 Aug 24;16(17):2836. doi: 10.3390/nu16172836.
BACKGROUND
Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM.
OBJECTIVES
Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS).
METHODS
Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results.
RESULTS
The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results.
CONCLUSIONS
There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.
背景
妊娠糖尿病（GDM）是最常见的妊娠问题之一，而维生素 D 与 GDM 之间的关系仍存在争议。
目的
我们旨在通过使用全基因组关联研究（GWAS）的汇总数据进行孟德尔随机化（MR）来研究维生素 D 与 GDM 之间的相关性。
方法
从 IEU OpenGWAS 项目中获取暴露和结局的数据，即维生素 D、维生素 D 不足和 GDM。使用逆方差加权（IVW）方法作为主要分析方法进行双向 MR 分析。本研究采用的补充方法包括加权中位数、简单模式、加权模式和 MR-Egger 回归。进行了一系列敏感性分析，以评估获得结果的可靠性。
结果
从 IEU OpenGWAS 项目中获取数据。在应用 MR 的三个假设后，13 个单核苷酸多态性（SNP）被纳入维生素 D 水平和维生素 D 缺乏与 GDM 的 MR 分析中，而 10 个和 26 个 SNP 分别被纳入 GDM 对维生素 D 水平和缺乏的分析中。IVW 分析的结果表明，维生素 D 水平与 GDM 之间存在显著正相关（OR = 1.057，95%CI：1.011-1.104， = 0.015）。相反，维生素 D 缺乏与 GDM 之间存在负相关（OR = 0.979，95%CI：0.959-0.999， = 0.039）。反向 MR 研究的结果表明，GDM 与维生素 D 之间不存在反向因果关系。多种 MR 方法的结果与 IVW 分析的方向一致。敏感性分析未发现异质性、多效性或异常值的证据，表明结果稳健。
结论
维生素 D 与 GDM 之间存在因果关系，维生素 D 水平是 GDM 的一个风险因素。
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