Association between Thyrotoxicosis and Gestational Diabetes Mellitus: A Mendelian Randomization Study

Yizhen Chen; Shaoxing  Guan; Xiaorong Su; Wei  Zhuang

doi:10.18502/ijph.v54i8.19580

Yizhen Chen Department of Pharmacy, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China
Shaoxing Guan School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
Xiaorong Su Department of Pharmacy, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China
Wei Zhuang Department of Pharmacy, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China

DOI: https://doi.org/10.18502/ijph.v54i8.19580

Keywords: Mendelian randomization; Gestational diabetes mellitus; Thyrotoxicosis; Insulin resistance

Abstract

Background: Insulin resistance and abnormal glucose metabolism are the main characteristics of thyrotoxicosis and gestational diabetes mellitus (GDM). However, it remains unclear whether thyrotoxicosis increases the risk of GDM. Therefore, this research aimed to explore the causality between thyrotoxicosis and GDM by using a Mendelian randomization (MR) analysis.

Methods: A MR analysis was conducted to explore the causal effects of thyrotoxicosis on GDM. Summary statistics data of thyrotoxicosis (3115 thyrotoxicosis cases and 187684 controls) and GDM (13039 cases and 197831 controls) were derived from genome-wide association study. We selected MR Egger, Weighted median, Inverse-variance weighted, Simple mode and Weighted mode to evaluate the causal effect between thyrotoxicosis and GDM.

Results: By using a two-sample MR analysis, we found a strong causal relationship between thyrotoxicosis and GDM as indicated by Inverse-variance weighted (OR=1.069; beta=0.067; 95%CI=1.023-1.118; P=0.003), Weighted median (OR=1.087; beta=0.084; 95%CI=1.040-1.137; P=0.0002), Simple mode (OR=1.102; beta=0.097; 95%CI= 1.038-1.170; P=0.013) and Weighted mode (OR=1.089; beta=0.085; 95%CI=1.033-1.147; P=0.013). No significant pleiotropy, heterogeneity, genetic correlations or bi-directional causal relationship was existed in this study. Bayesian colocalization suggested that thyrotoxicosis colocalized with GDM on rs10830963 (PP.H4 = 1.000), where rs10830963 was located on MTNR1B gene locus.

Conclusion: Thyrotoxicosis had a causal effect on the risk of developing GDM, and the exposure of thyrotoxicosis increased the risk of GDM.