多基因风险分数可移植性在遗传多样性人口中对常见疾病的可移植性
Sonia Moreno-Grau1,2, Manvi Vernekar3, Arturo Lopez-Pineda1,4,5
1Galatea Bio, Inc, 14350 Commerce Way, Miami Lakes, FL, 33146, USA.
Human genomics
|September 1, 2024
概括
多基因风险评分 (PRS) 显示,跨祖先的可移植性降低. 开发特定于祖先的模型可以提高PRS的性能,从而为不同人群提供更公平的风险预测.
科学领域:
- 遗传学和基因组学 在
- 精准医学是一门精准的医学.
- 人口健康 人口健康
背景情况:
- 在欧洲人群中开发的多基因风险评分 (PRS) 对其他祖先群体的概括性有限.
- 这种差异阻碍了PRS在疾病风险预测方面的全球临床应用.
- 调查跨不同祖先的PRS表现对于公平的医疗保健至关重要.
研究的目的:
- 评估各种PRS模型在非洲,欧洲,东亚和南亚人口中的可移植性.
- 将祖先特定的PRS模型与全球衍生模型的性能进行比较.
- 为了确定特定的条件,祖先定制的PRS可以提高临床效用.
主要方法:
- 将公开可用的PRS进行比较,并使用LDpred2,PRS-CSx和SNPnet.net开发了新的模型.
- 在英国生物库的欧洲数据上训练模型,并在不同的祖先队列上进行测试.
- 评估PRS可移植性和准确性,包括对独立数据集的验证和全现象协会研究 (PheWAS).
主要成果:
- 与基于欧洲的模型相比,在不同祖先之间应用时,PRS性能显著下降.
- 在所有评估组中,祖先特定的PRS模型显示出更好的预测准确性.
- 针对高血压和2型糖尿病等疾病的优化PRS在祖先之间显示了可比的性能.
结论:
- 对跨不同祖先的PRS模型进行全面评估对于选择合适的工具至关重要.
- 祖先特定的PRS模型对于提高非欧洲人群中的风险预测准确性和临床实用性至关重要.
- 这项工作支持为全球健康制定公平的PRS实施策略.
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