高多基因风险分类的不稳定性和通过整合性评分来减轻风险
medRxiv : the preprint server for health sciences
|August 30, 2024
概括
多基因风险评分 (PRS) 显示了各种高风险分类. 一种综合评分方法,ChronoAdd(Pubn),可以更一致地识别复杂特征的高风险个体.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 个性化医疗是个性化的医疗.
- 生物信息学是一种生物信息学.
背景情况:
- 多基因风险评分 (PRS) 在医疗保健和商业环境中越来越多地使用.
- 高多基因风险的分类在不同的PRS之间可能会有很大的差异.
- 需要稳定可靠的方法来识别高遗传风险的个体.
研究的目的:
- 评估三种复杂特征的编目PRS的关联和分类性能.
- 将个人最佳PRS (Best(Pubn)) 的分类一致性与整合性评分方法 (ChronoAdd(Pubn)) 进行比较.
主要方法:
- 按时间顺序排列与特征相关的出版物 (Pub n) 并为每一个确定单一最佳PRS (Best(Pub n)).
- 使用PRSmix框架生成ChronoAdd (Pub n) 评分,并随着时间的推移集成多个PRS.
- 评估了人口层面的关联强度和个人高风险分类 (前10%),无论是最佳 (Pub n) 还是ChronoAdd (Pub n) 评分.
主要成果:
- 个人最佳 (Pub n) 评分显示,总体而言,在人口层面上存在一致的关联,但在将个人归类为前10%风险组中存在很大差异.
- 与最佳Pubn) 评分相比,ChronoAdd (Pubn) 评分表现出更一致的高风险分类.
- 综合性评分方法提高了高风险个人识别的稳定性和可靠性.
结论:
- 综合性多基因风险评分方法 (ChronoAdd) 提供了更稳定和可靠的高风险个体的分类.
- 这种可适应的框架可以将新出现的PRS纳入其中,与当前的实施策略保持一致.
- 通过标准化高风险分层,ChronoAdd(Pubn) 方法提高了PRS的临床实用性.
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