Liao Wen-Ling, Hsieh Hao-I, Liu Ting-Yuan, Lu Hsing-Fang, Huang Yu-Chuen, Chang Ya-Wen, Tsai Fuu-Jen
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
Center for Personalized Medicine, Department of Medical Research, China Medical University Hospital, Taichung, 40447, Taiwan.
J Hum Genet. 2025 Aug 21. doi: 10.1038/s10038-025-01360-y.
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.
妊娠期糖尿病（GDM）是一种常见的妊娠并发症，受孕前超重或肥胖以及孕期体重增加过多（GWG）影响。本研究调查了体重指数（BMI）相关基因变异对台湾女性孕期体重增加和GDM风险的影响。一项针对3875名孕妇的病例对照研究，其中包括3162名根据口服葡萄糖耐量试验诊断为GDM的孕妇以及2483名有GWG数据的孕妇。对71848名女性进行全基因组关联研究以确定BMI相关基因变异，并计算了BMI的多基因风险评分（PRS_BMI）。PRS_BMI与GWG呈正相关（R² = 0.010，P < 0.001）。PRS_BMI每增加一个标准差，高GWG和GDM的比值比（OR）分别为2.28（95% CI = 2.03 - 2.55，P < 0.001）和1.34（95% CI = 1.24 - 1.45，P < 0.001）。分层分析表明，BMI < 25 kg/m²的女性中关联更强，而BMI≥25 kg/m²的女性中关联较弱。这些发现表明，PRS_BMI可用于识别孕期体重增加过多和GDM风险较高的女性，有助于早期监测和针对性的风险降低策略。
