Maternal GDM Status, Genetically Determined Blood Glucose, and Offspring Obesity Risk: An Observational Study

OBJECTIVE: The purpose of this study was to estimate the associations of genetically determined maternal blood glucose levels with obesity-related outcomes among children from pregnancies with and without gestational diabetes mellitus (GDM). METHODS: A total of 1,114 mothers with (N = 560) and without (N = 554) GDM and their children were included in the present study. A maternal genetic risk score (GRS) for blood glucose was constructed on the basis of 17 single-nucleotide polymorphisms identified from a recent genome-wide association study. RESULTS: It was found that maternal GRS for blood glucose showed different associations with offspring risk of overweight and obesity, as well as adiposity measures (all P (for interaction) < 0.05). Among mothers without GDM, genetically determined maternal blood glucose levels were associated with an 89% higher risk of overweight in their children (95% CI: 42%−152% per SD increase in GRS, P = 1.40 × 10(−5)) and a 120% higher risk of obesity (44%−235%, P = 2.61 × 10(−4)) after adjustment for covariates. In addition, higher maternal GRS for blood glucose was associated with children’s increased obesity-related traits (all P < 0.05). However, no significant associations were observed among children of mothers with GDM. CONCLUSIONS: This study indicates that GDM status may modify the relation between genetically determined glucose levels and obesity risk among children.