Associations between a polygenic risk score and the risk of gestational diabetes mellitus in a Chinese population: a case-control study

Abstract

Our objective was to construct a polygenic risk score (PRS) and assess its utility and effectiveness in predicting the risk of gestational diabetes mellitus (GDM) in a Chinese population. We performed a case-control study involving 638 patients with GDM and 1,062 healthy controls. Genotyping was conducted utilizing a genome-wide association study (GWAS), and a PRS was constructed. We identified 12 susceptibility loci that exhibited significant associations with the risk of GDM at a p-value threshold of ≤5.0 × 10^-8, of which four loci were newly discovered. A higher PRS was associated with an increased risk of GDM (OR: 1.44; 95% CI: 1.03, 2.01 for the highest quartile compared to the lowest quartile). The PRS demonstrated a clear linear relationship with the fasting plasma glucose (FPG), 1-hour postprandial glucose (1hPG), and 2-hour postprandial glucose (2hPG) levels. The maximally adjusted β coefficients and their corresponding 95% CIs were 0.181 (0.041, 0.320) for FPG, 0.225 (0.103, 0.346) for 1hPG, and 0.172 (0.036, 0.307) for 2hPG. Among the genetic variants examined, TCF7L2 rs7903146 displayed the strongest association with GDM risk (logOR = 0.18, p = 2.37 × 10^-19), followed by ADAMTSL1 rs10963767 (logOR = 0.14, p = 3.58 × 10^-15). The areas under the curve (AUCs) was significantly increased from 0.703 (0.678, 0.728) in the traditional risk factor model to 0.765 (0.741, 0.788) by including PRS. These findings indicate that pregnant women with a higher PRS could potentially derive considerable advantages from the implementation of a feasible PRS-based GDM screening program aimed at delivering precision prevention strategies within Chinese populations.

Keywords: Case-control study; Genome-wide association study; Gestational diabetes mellitus; Polygenic risk score.