多祖先多基因风险评分用于静脉血栓栓塞的风险
Yon Ho Jee1, Florian Thibord2,3, Alicia Dominguez4
1Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, United States.
Human molecular genetics
|June 16, 2024
概括
多祖先多基因风险评分 (PRSs) 显示出在不同祖先中识别有高风险的静脉血栓塞栓症 (VTE) 个体的希望. 这些先进的PRS可能会改善欧洲和非洲祖先人口的VTE风险预测.
科学领域:
- 遗传学 是一个遗传学.
- 心血管疾病流行病学
- 生物统计学 生物统计学
背景情况:
- 静脉血栓塞栓症 (VTE) 是疾病和死亡的主要原因,黑人和白人美国人之间发生的严重差异.
- 目前对VTE的多基因风险评分 (PRS) 主要基于欧洲祖先的遗传数据,这限制了它们在不同人群中的有效性.
- 训练在各种数据上的复杂,高维的PRS用于预测不同祖先的VTE风险的实用性需要进一步调查.
研究的目的:
- 开发和评估多祖先多基因风险评分 (PRSs) 进行静脉血栓栓塞 (VTE).
- 为了比较祖先特定的PRS与独立的欧洲和非洲祖先队列中的多祖先PRS的预测性能.
- 评估多祖先PRS的潜力,以改善各种人群中VTE风险分层.
主要方法:
- 构建了用于VTE的PRS,使用来自国际抗静脉血栓症网络 (INVENT) 财团GWAS的总结统计数据.
- 采用LDpred2和PRS-CSx方法来生成祖先特定和多祖先的PRS.
- 在独立的欧洲和非洲祖先测试样本中使用接收器操作曲线下的面积 (AUC) 评估PRS性能.
主要成果:
- 在欧洲祖先测试样本中,多祖先PRS略高于祖先特定的PRS (AUC0.609对比0.608).
- 在非洲祖先的测试样本中,多祖先的PRS也显示出比祖先特定的PRS更好的表现的趋势 (AUC0.59对0.58),尽管在统计学上并不显著.
- 表现最好的PRS的前五百分位与欧洲血统受试者的VTE风险增加1.9倍,非洲血统受试者的风险增加1.68倍.
结论:
- 多祖先的PRS显示出在不同祖先群体中增强VTE风险预测的潜力.
- 这些先进的PRS方法可以更好地识别患有VTE风险最高的人.
- 需要进一步的研究来完善多祖先PRS模型,以获得公平的VTE风险评估.
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