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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02796-z

摘要内容如下：

多基因风险评分（PRS）在预测性能方面有所改善，但在临床实施PRS之前，仍有几个挑战需要解决，包括PRS在不同人群中的预测性能降低，以及对提供者和患者的遗传结果的解释和沟通。为了应对这些挑战，美国国家人类基因组研究所（National Human Genome Research Institute）资助的电子医疗记录和基因组学（Emerge）网络开发了一个框架和管道，作为临床研究的一部分，向25，000名不同的成人和儿童提供基于PRS的基因组风险评估。从最初列出的23种情况中，根据PRS的性能、医疗可执行性和潜在的临床效用，选择了10种情况进行实施，包括心脏代谢疾病和癌症。在选择过程中考虑了标准化指标，并额外考虑了非洲裔和西班牙裔人口的证据强度。然后，我们开发了临床PRS实施的管道（分数转移到临床实验室，分数性能的验证和验证），并使用遗传祖先来校准PRS均值和方差，利用来自全美研究计划队列的13，475名参与者的遗传多样性数据来训练和测试模型参数。最后，我们创建了一个监管合规框架，并制定了一份PRS临床报告，以返回给提供者，并纳入额外的基因组风险评估。来自Emerge的初步经验可以为在不同的临床环境中实施基于PRS的测试所需的方法提供信息。

英文原文如下：

Abstracts

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.

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