EHR-based Genomic Discovery and Implementation (Pediatric Participants Supplement)

项目总结 在这份补充申请中，我们建议在Emerge IV工作的基础上再招聘250人 将在CLIA实验室(布罗德)接受基因组测试的青少年。因此，儿科研究队列位于 Mayo将由总共350名青少年参与者组成，参加社区儿科和青少年 医学诊所和当地学校。我们将估计4种疾病的多基因风险分数(PRS)，这些疾病会导致 严重的公共卫生负担，包括哮喘、肥胖、1型糖尿病和2型糖尿病。DNA将会是 被送去进行CLIA认证的基因组测试，我们将使用新的计算候选基因座或全基因组PR 使这些基因适应特定遗传祖先群体的方法。经过验证的PR将与家庭相结合 历史和临床风险评分，以创建全面的风险概况，并将报告给参与者和 提供者，并放置在电子健康记录(EHR)中，链接到临床决策支持(CDS)， 包括基于准则的风险管理信息。对于风险显著较高的参与者 至少发生4种疾病中的一种，结果将亲自披露，随后将评估 结果包括订购的新测试、降低风险的措施和可更改的风险因素的变化。我们的 对非典型肺炎的关注为人们带来了基因组药物。我们的具体目标包括：1)额外招聘250人 青少年参与者(总计350人)，他们将在CLIA实验室接受PRS的基因组测试；2) 通过与CDS的链接将PR集成到EHR中，CDS包含对医疗保健提供者的建议和 开发可扩展的方法，向参与者披露PrS结果；3)估计350种疾病中4种疾病的PrS 青少年参与者并计算全面的风险概况(包括PR)，以便返回给参与者； 4)在返回结果后对结果进行评估。

PROJECT SUMMARY In this supplemental application we propose to build on our work in eMERGE IV to recruit an additional 250 adolescents who will undergo genomic testing in a CLIA laboratory (Broad). Thus, the pediatric study cohort at Mayo will comprise a total of 350 adolescent participants attending the community pediatric and adolescent medicine clinic and local schools. We will estimate polygenic risk scores (PRSs) for 4 diseases that pose a significant public health burden including asthma, obesity, type 1 diabetes, and type 2 diabetes. DNA will be sent for CLIA-certified genomic testing, and we will calculate candidate loci or genome wide PRS using novel methods to adapt these to specific genetic ancestry groups. Validated PRS will be combined with family history and clinical risk scores to create comprehensive risk profiles that will be reported to participants and providers and placed in the electronic health record (EHR) with linkage to clinical decision support (CDS) that includes guideline-based risk-management information. For participants who are at significantly higher risk for developing at least 1 of the 4 diseases, results will be disclosed in-person followed by assessment of outcomes including new tests ordered, risk reduction measures, and changes in modifiable risk factors. Our focus on PRS brings genomic medicine to the population. Our specific aims include: 1) Recruit 250 additional adolescent participants (total n=350) who will undergo genomic testing for PRS in a CLIA laboratory; 2) Integrate PRS in the EHR with linkage to CDS that incorporates recommendations for healthcare providers and develop scalable methods for disclosing PRS results to participants; 3) Estimate PRS for 4 diseases in 350 adolescent participants and compute comprehensive risk profiles (that include PRS) for return to participants; 4) Assess outcomes following return of results.