人口表现和冠状动脉疾病的个人协议 多基因风险评分
medRxiv : the preprint server for health sciences
|August 7, 2024
概括
在人口层面上表现相似的冠状动脉疾病的多基因风险评分 (PRSs) 对个体风险预测的一致性较差. 这种不可靠性凸显了CAD PRSs临床实施的挑战.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 心血管疾病研究研究
- 生物信息学和计算生物学
背景情况:
- 冠状动脉疾病的多基因风险评分 (PRS) 在临床和商业环境中越来越多地使用.
- 评估不同CAD PRS用于个体风险预测的可靠性,对于临床实施至关重要.
研究的目的:
- 描述CAD PRS的可靠性,这些PRS在预测个人级别风险方面表现出相当于人口级别的性能.
- 评估各种CAD PRS在不同人群中的风险估计的一致性.
主要方法:
- 采用来自我们所有人研究计划 (AOU),宾夕法尼亚医学生物库 (PMBB) 和UCLA ATLAS精密健康生物库的数据进行的横截面研究.
- 对超过171,000名参与者计算了50个PRS,并使用Brier分数和AUROC评估了人口水平预测.
- 使用类内相关性 (ICC) 和Light's Kappa等效成绩的风险估计之间的评估个体级协议.
主要成果:
- 在171,095名AOU参与者中,50个PRS中48个显示出实际上相当于人口水平的预测.
- 在这些分数中,对个体风险预测的持续一致性很差 (ICC=0.351).
- 统计学上相当的分数之间的一致性是温和的 (ICC=0.649),而高风险值分配的一致性只有"公平" (Light's Kappa ≤0.56). 在PMBB和UCLA队伍中观察到类似的发现.
结论:
- 具有相当于人口水平性能的CAD PRS产生不可靠的个人风险估计.
- 对于CAD PRS的临床实施策略必须考虑到从看似相似的得分出发的潜在不一致的风险预测.
- 需要进行进一步的研究,以提高心血管疾病的个人水平PRS的准确性和一致性.
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