Assessment of potential risk factors associated with gestational diabetes mellitus: evidence from a Mendelian randomization study

Qingming Fu; Rumeng Chen; Shuling Xu; Yining Ding; Chunxia Huang; Binsheng He; Ting Jiang; Bin Zeng; Meihua Bao; Sen Li

doi:10.3389/fendo.2023.1276836

Assessment of potential risk factors associated with gestational diabetes mellitus: evidence from a Mendelian randomization study

Front Endocrinol (Lausanne). 2024 Jan 8:14:1276836. doi: 10.3389/fendo.2023.1276836. eCollection 2023.

Authors

Qingming Fu^#¹, Rumeng Chen^#², Shuling Xu^#², Yining Ding², Chunxia Huang¹, Binsheng He³, Ting Jiang¹, Bin Zeng¹, Meihua Bao^{3

4}, Sen Li²

Affiliations

¹ School of Stomatology, Changsha Medical University, Changsha, China.
² School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
³ The Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha, China.
⁴ Hunan key laboratory of the research and development of novel pharmaceutical preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China.

^# Contributed equally.

Abstract

Background: Previous research on the association between risk factors and gestational diabetes mellitus (GDM) primarily comprises observational studies with inconclusive results. The objective of this study is to investigate the causal relationship between 108 traits and GDM by employing a two-sample Mendelian randomization (MR) analysis to identify potential risk factors of GDM.

Methods: We conducted MR analyses to explore the relationships between traits and GDM. The genome-wide association studies (GWAS) for traits were primarily based on data from the UK Biobank (UKBB), while the GWAS for GDM utilized data from FinnGen. We employed a false discovery rate (FDR) of 5% to account for multiple comparisons.

Results: The inverse-variance weighted (IVW) method indicated that the genetically predicted 24 risk factors were significantly associated with GDM, such as "Forced expiratory volume in 1-second (FEV1)" (OR=0.76; 95% CI: 0.63, 0.92), "Forced vital capacity (FVC)" (OR=0.74; 95% CI: 0.64, 0.87), "Usual walking pace" (OR=0.19; 95% CI: 0.09, 0.39), "Sex hormone-binding globulin (SHBG)" (OR=0.86; 95% CI: 0.78, 0.94). The sensitivity analyses with MR-Egger and weighted median methods indicated consistent results for most of the trats.

Conclusion: Our study has uncovered a significant causal relationship between 24 risk factors and GDM. These results offer a new theoretical foundation for preventing or mitigating the risks associated with GDM.

Keywords: FinnGen; Mendelian randomization; UK biobank; gestational diabetes mellitus; risk factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes, Gestational* / epidemiology
Diabetes, Gestational* / genetics
Female
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Phenotype
Pregnancy
Risk Factors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the BUCM Precision Cultivation Program (Grant No. JZPY-202205) and the BUCM Research Development Fund (Grant No. 2021-ZXFZJJ-052).