多基因评分的准确性在遗传血统连续上有所不同
Yi Ding1, Kangcheng Hou2, Ziqi Xu3
1Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA. yiding920@ucla.edu.
Nature
|May 17, 2023
概括
多基因分数 (PGS) 显示基因祖先的准确性降低,甚至在群体内. 遗传距离比离散祖先标签更好地预测PGS的表现,突出了对连续性方法的需求.
科学领域:
- 遗传学
- 生物信息学
- 人口健康
背景情况:
- 多基因分数 (PGS) 对于预测疾病风险至关重要,但在不同人群中面临着可移植性的挑战.
- 目前对PGS可移植性的评估往往忽视了群体内的个体差异.
- 由于其有限的通用性,阻碍了保护产品保证制度的公平应用.
研究的目的:
- 研究遗传距离对不同祖先的多基因分数准确性的影响.
- 评估基因距离连续测量与PGS可移植性的离散祖先集群的有效性.
- 确定影响群体内和群体之间PGS表现的因素.
主要方法:
- 使用大型生物库 (ATLAS和英国生物库) 与多样化的参与者.
- 在一系列遗传祖先中评估PGS准确性.
- 使用皮尔森相关性量化遗传距离 (GD) 和PGS精度之间的关系.
- 欧洲和西班牙裔/拉丁裔美国人的PGS性能比较.
主要成果:
- PGS的准确性随着遗传祖先的连续性而下降,即使在表面上是同质的群体内也是如此.
- 基因距离 (GD) 与PGS准确度 (r = -0.95) 在84个特征之间有很强的相关性.
- 与训练数据相距较远的个体具有明显较低的PGS准确性.
- 在GD中最接近培训数据的西班牙裔/拉丁裔个体表现与远处的欧洲个体相似.
结论:
- 通过GD测量遗传祖先的连续性是PGS可移植性和准确性的关键因素.
- 独立的遗传祖先集群不足以准确评估和解释PGS的表现.
- 为了公平使用,未来的动物保护系统开发和应用必须考虑到基因变异的持续性质.
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