Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction

Area of Science:

• Human Genetics
• Reproductive Endocrinology
• Metabolic Diseases

Background:

• Gestational diabetes mellitus (GDM) is a significant pregnancy complication with increasing prevalence worldwide.
• Genetic predisposition plays a role in GDM development, but specific risk variants may differ across populations.
• Identifying genetic factors associated with GDM can aid in risk prediction and prevention strategies.

Purpose of the Study:

• To investigate the association between common genetic risk variants and GDM risk in a Russian cohort.
• To evaluate the effectiveness of selected single-nucleotide polymorphisms (SNPs) and a genetic risk score (GRS) in identifying GDM cases.

Main Methods:

• A case-control study involving 1,142 pregnant Russian women (688 GDM cases, 454 controls) was conducted.
• Eleven pre-selected single-nucleotide polymorphisms (SNPs) were genotyped using Taqman assays.
• Logistic regression and receiver operating characteristic (ROC) curve analysis were employed to assess associations and predictive utility.

Main Results:

• Two variants in the MTNR1B gene (rs1387153 and rs10830963) were significantly associated with increased GDM risk, even after adjusting for clinical covariates.
• The SNP rs10830963 showed a stronger independent association with GDM risk compared to rs1387153.
• Clinical variables alone predicted GDM risk (c-statistic 0.712), with modest improvements upon adding a GRS (0.719) or rs10830963 (0.729).

Conclusions:

• The study confirmed significant associations between two MTNR1B variants and GDM risk in Russian women, consistent with findings in other populations.
• Despite statistical significance, the investigated genetic variants, including the GRS, demonstrated limited clinical utility for the accurate identification of GDM cases.