评估冠心病多基因风险评分的表现和一致性
Sarah A Abramowitz1,2, Kristin Boulier3, Karl Keat4
1Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia.
JAMA
|November 16, 2024
概括
冠状动脉疾病的多基因风险评分 (PRS) 显示出类似的人群表现,但在个人层面上有很大差异. 这凸显了在临床实践中改善风险不确定性沟通方法的需要.
科学领域:
- 遗传学和基因组学
- 心血管疾病研究
- 精准医学
背景情况:
- 冠心病的多基因风险评分 (PRS) 越来越多地在临床和商业上使用.
- 现有CHDPRS的个人级别协议与人口级别的类似性能是不清楚的.
研究的目的:
- 评估冠状动脉疾病多基因风险得分 (PRS) 的个人水平一致性,这些得分表明在人口水平上具有可比性.
- 描述不同个人PRS风险预测的一致性.
主要方法:
- 一项横截面研究分析了来自我们所有人的研究计划 (AOU),宾夕法尼亚医学生物库 (PMBB) 和UCLA ATLAS精确健康生物库的数据.
- 已经计算出了48个CHD的PRS. 个人级别的协议使用类内相关系数 (ICC) 和Light κ进行了评估.
- 通过比较Brier分数和接收器运营商曲线下的面积来评估人口水平的表现.
主要成果:
- 虽然48个PRS中的46个显示出类似的人口水平预测,但个体水平的一致性很差 (ICC=0.373).
- 20%的参与者在不同PRS中分别处于最高和最低5%的风险类别.
- 通过对不同生物库的分析,获得了不同等级的分数,但缺乏个人层面的共识.
结论:
- 具有相似人群表现的冠心病PRS产生不一致的个体风险估计.
- 有效的临床使用需要方法来量化和传达与个人PRS预测相关的不确定性.
- 需要进一步的研究来完善PRS在患者护理中的解释和应用.
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