开发和验证1型糖尿病的跨祖先多基因风险评分
Basile Jumentier1, Hui-Qi Qu2, Tianyuan Lu3,4,5,6,7
1Research Center of the Sainte-Justine University Hospital, Université de Montréal, Montreal, QC, Canada.
Diabetologia
|March 7, 2026
概括
一种新的跨祖先多基因风险评分 (TA-PRS) 对于1型糖尿病显示,跨不同祖先的表现有所改善. 该工具增强了基因风险预测,有助于全民查和1型糖尿病早期干预策略.
科学领域:
- 遗传学 遗传学 是一个
- 流行病学 流行病学
- 生物统计学 生物统计学
背景情况:
- 1型糖尿病 (T1D) 具有很高的遗传性,使得多基因风险评分 (PRS) 对于风险查具有价值.
- 目前用于T1D的PRS,主要是使用欧洲数据开发的,在非欧洲人群中显示效率降低.
- 开发跨祖先的PRS对于在不同人群中进行公平有效的遗传风险评估至关重要.
研究的目的:
- 开发和验证1型糖尿病的跨祖先多基因风险评分 (TA-PRS),在多个祖先之间具有可比性能.
- 在非欧洲人群中改善现有的基于欧洲祖先的T1DPRS.
主要方法:
- 利用PRS-CSx方法与来自欧洲,东亚,非洲裔美国人和西班牙裔个体的全基因组关联研究数据 (N=29,469例).
- 通过结合非HLA成分 (超过一百万个变体) 和欧洲PRS (GRS2x) 的HLA成分,开发了一种TA-PRS.
- 在多祖先队列中使用接收器操作曲线下的面积 (AUROC),灵敏度和特异性评估PRS性能,并在独立队列中验证.
主要成果:
- 开发的TA-PRS在一个多祖先队列中,与欧洲的GRS2x (0.85) 相比,实现了显著更高的AUROC (0.89).
- TA-PRS在包括欧洲人 (0.71) 和南亚人 (0.77) 在内的各种祖先中表现出更好的灵敏度,超过了GRS2x (0.56在欧洲人中).
- 在所有祖先中,特异性仍然可以接受 (≥0.83),在四个独立队列中确认了验证.
结论:
- 一种针对1型糖尿病的新型跨祖先PRS (TA-PRS) 已成功开发,其性能优于现有的以欧洲为中心的模型.
- TA-PRS在不同的祖先中表现出可比的预测性能,支持其在全人口查计划中的实用性.
- 这一进步促进了1型糖尿病更公平的遗传风险分层,使得有针对性的监测和预防策略成为可能.
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