背景:许多研究已经检查了维生素D是否与妊娠期糖尿病(GDM)有关。然而,确定因果关系仍然具有挑战性,由于观察性研究和随机对照试验的一些缺点。
目的:对两个样本进行孟德尔随机化(MR),以研究25-羟基维生素D(25(OH)D)之间的潜在因果关系,维生素D结合蛋白(VDBP)和GDM风险。
方法:将来自独立队列的公开汇总数据用于两个样本的MR。对于25(OH)D,我们从英国生物银行获得了数据,IEU和EBI,然后进行荟萃分析以增强统计功效(通过METAL);对于VDBP,数据来自INTERVAL研究;对于GDM,数据来自FinnGen。采用逆方差加权(IVW)方法作为主要分析,再加上几个敏感性分析,比如MR-Egger,最大似然,加权中位数,和加权模式。
结果:IVW结果显示25(OH)D与GDM风险之间存在微弱的负因果关系[OR(95%CI)=0.71(0.50,0.99),p=0.046]。然而,根据敏感性分析,因果关系是不稳定的,Cochran的Q检验揭示了显著的异质性。在删除BMI相关的静脉注射后,25(OH)D与GDM之间的因果关系消失[OR(95%CI)=0.76(0.55,1.06),p=0.101]。此外,我们的研究没有证据支持VDBP水平与GDM风险因果关系相关的假设[OR(95%CI)=0.98(0.93,1.03),p=0.408]。
结论:根据这项研究,发现25(OH)D与GDM风险之间存在微弱的负因果关系,虽然我们几乎没有证据支持VDBP和GDM之间的联系。为了进一步探讨总或游离25(OH)D水平与GDM是否有因果关系,需要以育龄妇女和其他族裔群体为重点的GWAS数据。
BACKGROUND: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials.
OBJECTIVE: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk.
METHODS: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR-Egger, maximum likelihood, weighted median, and weighted mode.
RESULTS: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran\'s Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408].
CONCLUSIONS: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.