对心脏代谢特征的多基因风险评分证明了祖先对预测精准医学的重要性
Rachel L Kember1, Shefali S Verma, Anurag Verma
1Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19104, USA, rkember@pennmedicine.upenn.edu.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
|December 31, 2023
概括
多基因风险评分 (PRS) 使用多祖先数据表现更好,特别是对于非洲祖先的个人. 未来的研究应该专注于各种GWAS和普世PRS方法,以实现公平的精准医学.
科学领域:
- 遗传学 遗传学 是一个
- 基因组流行病学 基因组流行病学
- 精准医学是一门精准的医学.
背景情况:
- 多基因风险评分 (PRS) 对于预测疾病风险至关重要,但通常受全基因组关联研究 (GWAS) 的祖先特定训练数据的限制.
- 现有的PRS主要依赖于欧洲血统 (EUR) 队列,可能会限制它们在不同人群中的实用性.
研究的目的:
- 为了评估来自不同祖先群体的多祖先GWAS衍生的PRS的性能.
- 通过一项全现象关联研究 (PheWAS) 来评估PRS与各种表型的关联.
主要方法:
- 对于五种心脏代谢表型,利用了来自多祖先和祖先特定GWAS的PRS.
- 在宾夕法尼亚大学医学生物银行 (PMBB) 中,评估了非洲血统 (AFR) 和欧元 (EUR) 个体的PRS表现.
- 进行了PheWAS以确定具有广泛临床特征的PRS关联.
主要成果:
- 与祖先特定的PRS相比,多祖先PRS在AFR个体中对大多数心脏代谢表型的效果大小有所改善.
- 来自多祖先数据的PRS在各种祖先群体中表现出强度.
- 观察到与许多表型有显著的PRS关联,包括心血管和代谢疾病,在AFR和EUR组之间有不同的模式.
结论:
- 多祖先GWAS数据提高了PRS的性能,特别是在代表性不足的人群中.
- 为公平的精准医学开发通用,国际化的PRS是必要的.
- 优先考虑多样化的GWAS和包容性的PRS方法对于全球推进个性化医疗保健至关重要.
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