GeNYC: Genomic Implementation Research in the Diverse Settings and Populations of New York City

实施基因组医学改变医疗保健和改善健康的承诺将不会 直到发现与不同人群和临床医生相关并可供其使用 关心他们的人。我们的GeNYC团队准备帮助医学基因组学成为一种创新的、 以包容、健康和健康公平为核心的协作纪律。我们有几十年的经验 动员不同的利益相关者-研究人员、患者、临床医生、倡导者和企业家-进行 我国大型卫生系统和安全网中的慢性病预防和控制临床试验 诊所。在我们最近的16次试验中 小气 已完成或正在进行的，80%包括初级保健或社区站点， 732名参与者/研究，69%是非洲血统(AA)或拉丁裔，17%拒绝，我们保留了84%。 我们选择利用这一专业知识来进行基因组实施研究。在我们团队的核心 是基因组学利益相关者董事会。我们一起进行了GUARDD，一项多站点实用临床试验(PCT) 研究将遗传风险信息纳入初级保健的效果和挑战。我们测试了戒酒协会的成年人 有高血压、无糖尿病或慢性肾脏疾病(CKD)的APOL1高危变种几乎 仅限于AAA，这会使肾衰竭风险增加10倍。我们从15个社区招募了2052名AA成年人 纽约市的学术初级保健实践，训练有素的非专业工作人员将APOL1结果返回给患者并提醒 临床医生通过电子健康记录(EHR)中的临床决策支持来了解结果。我们的联合初选 结果：在那些被告知患有高血压的人中，3米处的收缩压(SBP)(保留率为93%)降低了6毫米汞柱 高危载脂蛋白1型与3毫米汞柱相比，如果被告知是低危的(p=0.008)。 我们现在准备并承诺加入IGNITE II并在#年进行基因组实施PCTS 不同的环境和人群。为此，我们召集了一个跨学科的团队，并研究 载脂蛋白1风险信息对包括CKD在内的AA患者更广泛表型的影响 患肾衰竭的风险更高，而且往往没有得到初级保健提供者的诊断。我们的目标是：(1) 作为IGNITE2的增强多样性位点，促进患者招募和保留到基因组中 实施PCTS；以及(2)实施GUARDD-US，这是一个将GUARDD扩展到AA的全网PCT 没有CKD的患者和患有CKD的患者以及不同患者和提供者人群的其他点燃部位。我们会 随机对患者进行APOL1检测与等待名单对照，并评估对SBP、肾脏诊断、成本的影响 有效性和心理行为结果，因此结果可以为临床医生、政策制定者和 付款人。如果成功，GeNYC可能会为未来实施基因组学的努力提供一个强大的框架 医学在不同的临床实践中，验证APOL1对高血压AA患者的风险知情管理 在肾衰竭风险较高的情况下，为消除以下方面的种族、民族和祖先差异作出重要努力 健康，并表明弱势群体可以最先从基因组发现中受益。

The promise of genomic medicine implementation transforming healthcare and improving health will not be realized until discoveries become relevant to and available for use by diverse populations and the clinicians who care for them. Our GeNYC team is prepared to help medical genomics become an innovative, collaborative discipline with inclusiveness, health and health equity at its core. We have decades of experience engaging diverse stakeholders- researchers, patients, clinicians, advocates and entrepreneurs- to conduct chronic disease prevention and control clinical trials in our large health system and network of safety net clinics. In our 16 trials recently mean completed or underway, 80% included primary care or community sites, with a 732 participants/study, 69% were African ancestry (AA) or Latino, 17% refused, and we retained 84%. We chose toharness this expertise to conduct genomic implementation research. At the heart of our team is a Genomics Stakeholder Board. Together, we conducted GUARDD, a multi-site pragmatic clinical trial (PCT) to study effects and challenges of incorporating genetic risk information into primary care. We tested AA adults with hypertension, without diabetes or chronic kidney disease (CKD) for APOL1 high-risk variants nearly exclusive to AAs, that increase kidney failure risk 10-fold. We recruited 2052 AA adults from 15 community and academic primary care practices in NYC, trained lay staff who returned APOL1 results to patients and alerted clinicians of results through clinical decision support in electronic health records (EHRs). Our co-primary outcome, systolic blood pressure (SBP) at 3m (retention rate 93%) reduced by 6mmHg in those told they had high-risk APOL1 genotypes vs. 3mmHg if told they were low-risk (p=0.008). We are now prepared and committed to join IGNITE II and conduct genomic implementation PCTs in diverse settings and populations. We brought a transdisciplinary team together for this purpose, and to study the impact of APO1 risk information on a broader phenotype of AA patients, including those with CKD, who have even higher risk for kidney failure and are often undiagnosed by primary care providers. We aim to: (1) Serve as an enhanced diversity site for IGNITE2, facilitating recruitment and retention of patients into genomic implementation PCTs; and (2) Conduct GUARDD-US, a network-wide PCT expanding GUARDD to AA patients without and with CKD and to other IGNITE sites with different patient and provider populations. We will randomize patients to APOL1 testing vs. waitlist control, and evaluate impact on SBP, renal diagnosis, cost effectiveness and psycho-behavioral outcomes, so results can inform decisions by clinicians, policymakers and payers. If successful, GeNYC may provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices, validate APOL1 risk-informed management of hypertensive AA patients at high risk of kidney failure, contribute to important efforts to eliminate racial, ethnic and ancestral disparities in health, and show that vulnerable populations can be the first to benefit from genomic discoveries.