Clinical use of polygenic risk scores (PRSs) can potentially improve health outcomes, but there are many open questions about how to implement PRSs effectively and equitably in primary care. To further these goals, Lennon et al. developed a pipeline within the Electronic Medical Records and Genomics (eMERGE) Network, consisting of diverse patients drawn from the US population, to perform polygenic risk assessment for ten common diseases and return these results to healthcare providers and patients. The authors outline the procedures used to optimize and validate PRSs for each disease across different ancestry groups and to calibrate the resulting z-scores based on the genetically inferred ancestry of each study participant. They also describe the pipeline used to generate each individualized clinical report, which includes a qualitative framework to indicate diseases for which a high PRS was found. Among the first 2,500 individuals assessed using this pipeline, they identified 581 individuals with a high PRS for at least one of the ten conditions. Future studies will be needed to assess whether return of these PRS results can be leveraged to improve health outcomes through appropriately tailored interventions for disease prevention or early detection.

Original reference: Nat. Med. 30, 480–487 (2024)

多基因风险评分 (PRS) 的临床使用可能会改善健康结果，但如何在初级保健中有效、公平地实施 PRS 仍存在许多悬而未决的问题。为了进一步实现这些目标，列侬等人。在电子病历和基因组学 (eMERGE) 网络内开发了一个管道，由来自美国人口的不同患者组成，对十种常见疾病进行多基因风险评估，并将这些结果返回给医疗保健提供者和患者。作者概述了用于优化和验证不同血统群体中每种疾病的 PRS 的程序，并根据每个研究参与者的遗传推断血统来校准所得的z分数。他们还描述了用于生成每个个性化临床报告的流程，其中包括一个定性框架，用于指示已发现高 PRS 的疾病。在使用此管道评估的前 2,500 名个人中，他们确定了 581 名个人在 10 种情况中至少有一种具有高 PRS。未来的研究需要评估这些 PRS 结果的返回是否可以通过适当定制的疾病预防或早期检测干预措施来改善健康结果。

原文参考： Nat.医学。 30、480–487 (2024)