The impact of educational attainment on gestational diabetes mellitus is mediated by body mass index: A Mendelian randomization study

Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and neonatal outcomes. While numerous studies have investigated the factors influencing GDM, the relationship between educational attainment and the GDM risk remains less explored. This study employs a Mendelian randomization (MR) approach to estimate the causal relationship between educational attainment, as a proxy for socioeconomic inequality, and the risk of GDM, and to quantify the roles of body mass index (BMI) as a potential mediator. We performed a two-sample MR study of genetically predicted educational attainment (instrumented using 1271 variants from 766,345 individuals) and gestational diabetes mellitus (116,363 individuals) using the largest genome-wide association studies. We used a two-step MR to quantify the proportion of education's effect on GDM mediated by BMI (681,275 individuals). Each standard deviation increase in educational attainment (4.2 years of schooling) was protective of GDM (odds ratios: 0.67; 95% confidence intervals [CI]: 0.59, 0.76). Higher educational attainment was also protective for BMI [β = -0.27 standard deviation (~1.3 kg/m2); 95% CI: -0.32, -0.22]. BMI mediated 35% (95% CI: 25%, 46%) of the total effect of education on GDM. Higher educational attainment has a protective effect on GDM risk. Interventions to reduce excess adiposity at the population level may reduce this risk, but the effect of education on GDM remains largely unexplained. Further investigation is necessary to identify additional risk factors that function as potentially modifiable mediators.