Dataset Information

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

ABSTRACT: OBJECTIVE: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. STUDY DESIGN: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). STUDY POPULATION:Among Caucasian women, we identified 458 cases of GDM and 1538 pregnant controls with normal glucose tolerance. RESULTS: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). CONCLUSIONS: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.

SUBMITTER: Kawai VK

PROVIDER: S-EPMC5533106 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kawai V K VK Levinson R T RT Adefurin A A Kurnik D D Collier S P SP Conway D D Stein C M CM

Clinical endocrinology 20170526 2

<h4>Objective</h4>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.<h4>Study design</h4>We conducted a case-control study using the Vanderbilt Medical Center biobank (BioVU) and calculated ...[more]

PMID: 28429832

Similar Datasets

Project description:ObjectiveWe aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases.MethodsWe conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations.ResultsTwo variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764).ConclusionAmong 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets