Polygenic risk score as a tool to predict gestational weight gain and gestational diabetes among pregnant women in Taiwan.

Abstract

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication influenced by pre-pregnancy overweight or obese and high gestational weight gain (GWG). This study investigated the impact of body mass index (BMI)-related genetic variants on GWG and GDM risk among Taiwanese women. A case-control study of 3875 pregnant women included 3162 with GDM based on oral glucose tolerance tests and 2483 with GWG data. A genome-wide association study of 71,848 women identified BMI related genetic variants, and a polygenic risk score for BMI (PRS_BMI) was calculated. PRS_BMI was positively associated with GWG (R² = 0.010, P < 0.001). The odds ratio (ORs) for high GWG and GDM per standard deviation increase in PRS_BMI were 2.28 (95% CI = 2.03-2.55, P < 0.001) and 1.34 (95% CI = 1.24-1.45, P < 0.001), respectively. Stratified analyses indicated stronger associations in women with BMI < 25 kg/m², while weaker associations were observed in those with BMI ≥ 25 kg/m². These findings suggest PRS_BMI could be used to identify women at higher risk for excessive GWG and GDM, aiding in early monitoring and targeted risk-reduction strategies.