The gdM-OMics Study: A Personalized Epigenetic Approach to Early Gestational Diabetes Diagnosis

Gestational diabetes is becoming a major health problem globally where it poses an increased risk of pre- and postnatal complications in both the mother and the fetus. Intrauterine hyperglycemia causes higher perinatal mortality as well as an increased rate of excessive birth weight, preterm birth, and respiratory distress syndrome. Women who develop gestational diabetes during pregnancy are at a greater risk of type 2 diabetes in later life. Similarly, their children are predisposed to a lifelong risk of obesity in addition to metabolic and cardiovascular diseases. Currently, GDM diagnosis is performed late during the second trimester (24-28 weeks of gestation) using an Oral Glucose Tolerance Test (OGTT). Nevertheless, late diagnosis leads to reduced treatment efficacy and increased complications despite therapy. Accurate approaches for early diagnosis are still lacking, therefore research in this direction is urgently needed. To identify suitable methods for early GDM prediction, we will perform the first large-scale genome-wide DNA methylation screening in pregnant women before and after GDM onset. Using this data, we will identify differentially methylated regions (DMRs), which will allow us to develop methylation risk scores and machine learning models for early GDM prediction. We will perform DNA methylation screening in samples collected at the Women's Wellness and Research Center (WWRC) of Hamad Medical Corporation (HMC). We will later validate our findings and test the accuracy of our models using the Qatar Birth Cohort Study (QBiC). Next, we will determine whether epigenetic alterations associated with GDM pathogenesis affect similar genes or pathways in women with Type 2 Diabetes. Here, we will compare GDM-related DMRs to those identified following an epigenome-wide association study (EWAS) on Qataris with T2D. We strongly believe that this research will improve our understanding of epigenetic alterations in GDM and enable the discovery of novel disease mechanisms as well as potential risk predictors. Considering the high rates of gestational diabetes, such discoveries will be highly valuable to the health and well-being of women and children in Qatar.

Hamad Bin Khalifa University (HBKU)