OBJECTIVE Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women. RESEARCH DESIGN AND METHODS Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility. RESULTS Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (−0.08 vs. 0.31, P = 2.3 × 10−11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05–2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15–0.49, P = 3.0 × 10−4). Although there was variation, a similar trend was observed across study cohorts. CONCLUSIONS In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.

中文翻译：

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全基因组多基因风险评分可预测有妊娠糖尿病史的女性发生 2 型糖尿病的风险


目的 有妊娠糖尿病 (GDM) 病史的女性患 2 型糖尿病 (T2D) 的风险增加。目前尚不清楚遗传信息是否可以改善这些女性 T2D 事件的预测。研究设计和方法 使用代表四个不同血统的五个独立队列 (n = 1,895)，我们研究了全基因组 T2D 多基因风险评分 (PRS) 是否与 T2D 事件风险增加相关。我们还计算了将 T2D PRS 纳入临床风险模型后的受试者工作特征曲线下面积 (AUROC) 和连续净重分类改善 (NRI)，以评估诊断效用。结果 在 1,895 名有 GDM 病史的女性中，363 名 (19.2%) 在 2 至 30 年内患上 T2D。 T2D 患者的 T2D PRS 较高（−0.08 vs. 0.31，P = 2.3 × 10−11），并且与 T2D 发生风险增加相关（优势比每增加 1-SD 1.52，95% CI 1.05–2.21） ，P = 0.03）。在一个包含年龄、糖尿病家族史、收缩压和 BMI 的模型中，PRS 的纳入导致 T2D 的 AUROC 从 0.71 增加到 0.74，NRI 得到中等程度的改善（0.32，95% CI 0.15-0.49） , P = 3.0 × 10−4)。尽管存在差异，但在研究队列中观察到了类似的趋势。结论 在具有不同血统的 GDM 女性队列中，T2D PRS 与 T2D 的未来发展显着相关。当 T2D PRS 集成到临床风险模型中以预测 T2D 事件时，AUROC 观察到显着但微小的改进。