Implementing and Evaluating Genetic Screening in Healthy Adults for Precision Public Health

摘要 在美国，数以百万计的人在不知情的情况下携带了林奇综合征(LS)的致病基因变异， 遗传性乳腺癌和卵巢癌(HBOC)和家族性高胆固醇血症(FH) 严重但可预防疾病的风险大大增加。对于这些遗传疾病，指南- 如果知道这一点，建议的预防性卫生服务可能会减少相关的发病率和死亡率 潜在的遗传风险是可用的。然而，这些人中有一半以上仍然身份不明或 只有在他们或相当数量的亲属被诊断出患有危及生命的疾病后才能确认 疾病。这意味着错失了预防疾病的机会。为此，美国国家科学院 科学、工程和医学的基因组学和公共卫生行动合作提供了路线图 用于群体基因筛查计划，以改善对临床上患有这些疾病的个人的识别 可行的条件。从2021年6月开始，北卡罗来纳大学(UNC)精密项目 医疗保健中的医学正在试行一项基于遗传学的临床服务，以筛查与 LS、HBOC和FH，称为UNC精密健康基因筛查测试。这一临床服务提供了 研究在健康人群中实施基于遗传学的筛查计划的理想机会。至 为此，我们建议(1)审查北卡罗来纳大学精密健康基因筛查的实施结果 (2)确定和调整实施北卡罗来纳大学精密健康基因筛查测试的战略； 以及(3)检查北卡罗来纳大学精密健康基因筛查测试对患者结局的影响。这个 这项建议的目的是为了更好地了解和借鉴UNC Precision的实施 健康基因筛查测试，为在不同的，真实的， 世界临床环境。此外，这些发现将直接为未来要检验的假设的发展提供信息。 UNC精密健康基因筛查试验对患者健康结局的影响及关键 通过未来的第二类混合有效性研究取得的执行成果。通过这一系列研究， 我们可以更好地了解基于遗传学的筛查计划的实施和有效性。这 基础性的理解将为未来的工作提供信息，以实现人人享有精确健康的承诺。

Abstract In the US, millions of people unknowingly carry pathogenic genetic variants for Lynch syndrome (LS), Hereditary Breast and Ovarian Cancer (HBOC), and Familial Hypercholesterolemia (FH), which confer substantially-elevated risks of serious yet preventable diseases. For these genetic conditions, guideline- recommended preventive health services might reduce associated morbidity and mortality if knowledge of this underlying genetic risk is available. However, more than half of these individuals remain unidentified or are identified only after they or a significant number of relatives have been diagnosed with life-threatening diseases. This represents a missed opportunity to prevent disease. For this reason, National Academies of Sciences, Engineering and Medicine’s Genomics and Public Health Action Collaborative provided a roadmap for population genetic screening programs to improve identification of individuals with these clinically actionable conditions. Beginning June 2021, University of North Carolina (UNC) Program for Precision Medicine in Healthcare is piloting a clinical offering for genetics-based screening for the genes associated with LS, HBOC and FH, called the UNC Precision Health Genetic Screening Test. This clinical offering provides the ideal opportunity to study the implementation of a genetics-based screen program in a healthy population. To this end we propose to (1) examine implementation outcomes of the UNC Precision Health Genetic Screening Test; (2) identify and tailor strategies for the implementation of UNC Precision Health Genetic Screening Test; and (3) examine the impact of the UNC Precision Health Genetic Screening Test on patient outcomes. The objective of this proposal is to better understand and learn from the implementation of the UNC Precision Health Genetic Screening Test to inform implementation of precision health genetic screening in diverse, real- world clinical settings. Further, these findings will directly inform the development of future hypotheses to test the effect of the UNC Precision Health Genetic Screening Test on patient health outcomes and key implementation outcomes through a future Type II Hybrid Effectiveness study. Through this line of research, we can better understand the implementation and effectiveness of a genetics-based screening program. This foundational understanding will inform future work to achieve the promise of precision health for all.