25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study

Yiwen Qiu; Diliyaer Ainiwan; Ye Huang; Libi Zhang; Haoyue Cheng; Xialidan Alifu; Haibo Zhou; Nuo Xv; Boya Wang; Shuhui Wang; Zexin Chen; Hui Liu; Danqing Chen; Yunxian Yu

doi:10.3390/nu16162603

25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study

Nutrients. 2024 Aug 7;16(16):2603. doi: 10.3390/nu16162603.

Authors

Yiwen Qiu^{1

2}, Diliyaer Ainiwan^{1

2}, Ye Huang^{1

2}, Libi Zhang^{1

2}, Haoyue Cheng^{1

2}, Xialidan Alifu^{1

2}, Haibo Zhou^{1

2}, Nuo Xv^{1

2}, Boya Wang^{1

2}, Shuhui Wang^{1

2}, Zexin Chen³, Hui Liu⁴, Danqing Chen⁵, Yunxian Yu^{1

2}

Affiliations

¹ Department of Public Health and Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
² Department of Epidemiology and Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou 310058, China.
³ Center of Clinical Epidemiology and Biostatistics, Department of Scientific Research, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
⁴ Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
⁵ Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd #1, Hangzhou 310006, China.

Abstract

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.

Keywords: 25(OH)D; Mendelian randomization; Vitamin D; Vitamin D binding protein; gestational diabetes mellitus.

Publication types

Meta-Analysis

MeSH terms

Diabetes, Gestational* / blood
Diabetes, Gestational* / genetics
Female
Humans
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide
Pregnancy
Risk Factors
Vitamin D* / analogs & derivatives
Vitamin D* / blood
Vitamin D-Binding Protein* / blood
Vitamin D-Binding Protein* / genetics

Substances

Vitamin D-Binding Protein
Vitamin D
25-hydroxyvitamin D
GC protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding