A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes

Gestational diabetes (GDM) is characterized by maternal glucose intolerance that manifests during pregnancy. Because GDM resembles type 2 diabetes (T2DM), shared genetic predisposition is likely but has not been established. We tested the hypothesis that a genetic risk score (GRS) that included variants known to be associated with T2DM is associated with GDM.

We conducted a case-control study using the Vanderbilt Medical Center biobank (BioVU) and calculated a simple-count GRS using 34 variants previously associated with T2DM or fasting glucose in the general population, or with GDM or glucose intolerance in pregnancy. We assessed the association of the GRS with GDM adjusting for maternal age, parity, and body mass index (BMI) and calculated the area under the curve for the receiver-operating characteristic curve (c-statistic).

Among Caucasian women, we identified 458 cases of GDM and 1538 pregnant controls with normal glucose tolerance.

Cases of GDM had a higher number of risk alleles compared to controls (38.9±4.0 vs 37.4±4.0 risk alleles, P=1.6×10^-11 ). The GRS was significantly associated with GDM; the adjusted odds ratio associated with each additional risk allele was 1.10 (95% CI: 1.07-1.13, P=6×10^-11 ). Clinical variables predicted the risk of GDM (c-statistic 0.67, 95% CI: 0.64-0.70), and adding the GRS modestly improved prediction (0.70, 95% CI: 0.67-0.73).

Among Caucasian women, a GRS that included common T2DM genetic risk variants was associated with increased risk of GDM but showed limited utility in the identification of GDM cases.