Published online Sep 16, 2024. doi: 10.12998/wjcc.v12.i26.5937
Revised: July 1, 2024
Accepted: July 10, 2024
Published online: September 16, 2024
Processing time: 87 Days and 11.1 Hours
Although there is currently a wealth of evidence to indicate that maternal educational attainment is associated with gestational diabetes mellitus (GDM), the specific modifiable risk factors that mediate the causal relationship between these two variables have yet to be identified.
To identify the specific modifiable risk factors that mediate the causal relationship between the level of maternal education and GDM.
Mendelian randomization (MR) was conducted using data from genome-wide association studies of European populations. We initially performed a two-sample MR analysis using data on genetic variants associated with the duration of education as instruments, and subsequently adopted a two-step MR approach using metabolic and lifestyle factors as mediators to examine the mechanisms underlying the relationship between the level of maternal education and risk of developing GDM. In addition, we calculated the proportions of total causal effects mediated by identified metabolic and lifestyle factors.
A genetically predicted higher educational attainment was found to be associated with a lower risk of developing GDM (OR: 0.71, 95%CI: 0.60-0.84). Among the metabolic factors assessed, four emerged as potential mediators of the education-GDM association, which, ranked by mediated proportions, were as follows: Waist-to-hip-ratio (31.56%, 95%CI: 12.38%-50.70%), body mass index (19.20%, 95%CI: 12.03%-26.42%), high-density lipoprotein cholesterol (12.81%, 95%CI: 8.65%-17.05%), and apolipoprotein A-1 (7.70%, 95%CI: 4.32%-11.05%). These findings proved to be robust to sensitivity analyses.
Our findings indicate a causal relationship between lower levels of maternal education and the risk of developing GDM can be partly explained by adverse metabolic profiles.
Core Tip: Studies have shown that the level of maternal education is associated with the risk of developing gestational diabetes mellitus (GDM). In this study, we sought to identify the specific modifiable risk factors that mediate the causal relationship between the level of maternal education and the likelihood of developing GDM. We performed Mendelian randomization analyses based on publicly available data obtained in a number of genome-wide association studies of European populations. Our findings indicate that a genetically predicted higher level of maternal education is associated with a lower GDM risk and that four modifiable metabolic factors contribute to mediating this association, namely, waist-to-hip ratio, body mass index, and the contents of high-density lipoprotein cholesterol and apolipoprotein A-1.