Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRSs in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. The study processes used to test patients, report their PRS results to them and their primary care providers (PCPs), and promote the use of those results in clinical decision-making are modeled on common practices in primary care. The following diseases were chosen for their prevalence and familiarity to PCPs: coronary artery disease; type 2 diabetes; atrial fibrillation; and breast, colorectal, and prostate cancers. A randomized clinical trial (RCT) design and primary outcome of time-to-new-diagnosis of a target disease bring methodological rigor to the question of the clinical utility of PRS implementation. The study’s pragmatic RCT design enhances its relevance to how PRS might reasonably be implemented in primary care. Steps the study has taken to promote health equity include the thoughtful handling of genetic ancestry in PRS construction and reporting and enhanced recruitment strategies to address underrepresentation in research participation. To date, enhanced recruitment efforts have been both necessary and successful: participants of underrepresented race and ethnicity groups have been less likely to enroll in the study than expected but ultimately achieved proportional representation through targeted efforts. The GenoVA Study experience to date offers insights for evaluating the clinical utility of equitable PRS implementation in adult primary care.

中文翻译：

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GenoVA 研究：在初级保健中公平实施多基因风险评分的务实随机试验

多基因风险评分（PRS）有望用于疾病风险评估和预防。退伍军人事务部的基因组医学 (GenoVA) 研究正在解决预防性护理中 PRS 临床实施的三个主要挑战：定义和确定其临床效用、在时间有限的初级保健环境中实施它们，以及应对其加剧医疗保健差距的可能性。用于测试患者、向患者及其初级保健提供者 (PCP) 报告 PRS 结果以及促进这些结果在临床决策中的使用的研究过程以初级保健中的常见做法为蓝本。根据 PCP 的患病率和熟悉程度，选择以下疾病： 冠状动脉疾病； 2型糖尿病;心房颤动;以及乳腺癌、结直肠癌和前列腺癌。随机临床试验 (RCT) 设计和目标疾病新诊断时间的主要结果为 PRS 实施的临床效用问题带来了方法学上的严谨性。该研究务实的 RCT 设计增强了其与如何在初级保健中合理实施 PRS 的相关性。该研究为促进健康公平而采取的措施包括在 PRS 构建和报告中深思熟虑地处理遗传血统，以及加强招募策略以解决研究参与代表性不足的问题。迄今为止，加强招募工作既是必要的，也是成功的：代表性不足的种族和族裔群体的参与者参加研究的可能性低于预期，但最终通过有针对性的努力实现了比例代表性。迄今为止的 GenoVA 研究经验为评估成人初级保健中公平 PRS 实施的临床效用提供了见解。