Polygenic Risk Scores for Healthier African American Families

项目摘要 为了促进儿童的健康和护理，如eMERGE II和III，CCHMC将在 eMERGE IV，在怀孕或最近分娩的自我认定的非洲裔美国人（AA）妇女中确定， 他们的孩子，沿着着愿意的父亲和兄弟姐妹。eMERGE IV系列将是 一项新的CCHMC计划，一个名为“我的基因组和我”的母亲和婴儿配对出生队列，辛辛那提 （MGMC），旨在发展对告知健康和疾病风险的基因组学的理解， 在出生时并持续整个生命周期，在入组时随机进行基因分型， 结果是新生儿或更大的儿童。我们的eMERGE IV项目将直接解决道德问题， 通过将结果返回给对婴儿、兄弟姐妹和父母进行不同考虑的家庭来提高 关于正在研究的特定表型。对于eMERGE IV，作为位点特异性表型，我们提名 哮喘、特应性皮炎、肥胖、高胆固醇血症、高血压、早产和乳腺癌。我们 将利用所做的工作，使开发多基因风险评分（PRS）和基因组风险估计 除了eMERGE IV网络选择的15种其他条件外， 在整个网络内就所采用的减贫战略和绿色环境报告达成共识。对家庭的照顾将利用 成人和儿科医院之间的电子健康记录的协调， 通过母婴数据中心（MIDH）利用观察性医疗成果伙伴关系实现 （OMOP）通用数据模型。对于数据质量控制，我们将评估eMERGE IV之间的差异 基因分型和低读取深度覆盖（LRDC）基因型（LRDC测序将由CCHMC承担费用。） 我们将收集我们当地AA社区对基因组结果和回报的偏好和态度 的结果。我们将制定降低健康风险的建议，并在可采取行动和不可采取行动的情况下退回GRE。 减贫战略，以评估减贫战略对遵守减轻风险建议的影响。我们将使用SMART 关于FHIR（可替代医疗应用、可重复使用技术和快速医疗保健互操作性） 资源）通过电子健康记录（EHR）-集成临床决策支持（CDS）-Hooks 为成人和儿童EHR系统提供CDS的框架。我们会定期修订生产者责任计划， GRES并在指示时返回更改。CCHMC将提供来自> 17，000个DNA AA的LRDC测序 来自CCHMC生物样本库中儿童的样本和总计≥ 50，000例受试者用于基因型生成， 线粒体DNA变异分析。联合地理编码将可用于CCHMC的所有eMERGE IV研究中心。 为了在CCHMC内传播基因组实践，在整个网络中，CCHMC将提供 服务，以推进特定条件下的PRS和GR，从急性淋巴细胞白血病，偏头痛， 头痛和自杀。总之，CCHMC提出了一个积极的计划，利用基因组医学来促进 更好的健康结果，重点是服务不足的AA新生儿和母亲与他们的家人的二人组。

PROJECT ABSTRACT To advance the health and care of children, as in eMERGE II & III, CCHMC will assemble a birth cohort in eMERGE IV, ascertained on pregnant or recently delivered self-identified African-American (AA) women and their babies, along with the willing fathers and siblings. The eMERGE IV collection will be the inaugural effort in a new CCHMC initiative, a birth cohort of mother and baby dyads called My Genome and Me, Cincinnati (MGMC), conceived to develop an understanding of the genomics that informs health and disease risk, beginning at birth and continuing across the lifespan with dyads randomized at enrollment to genotyping with return of results as neonates or later as older children. Our eMERGE IV project will directly grapple with the ethical issues raised by return of results to families with different considerations operating in babies, siblings and parents regarding the particular phenotypes being studied. For eMERGE IV, as site-specific phenotypes, we nominate Asthma, Atopic Dermatitis, Obesity, Hypercholesterolemia, Hypertension, Prematurity, and Breast Cancer. We will exploit the work done that will enable developing polygenic risk scores (PRSs) and genomic risk estimates (GREs) for these conditions in addition to the 15 others chosen by the eMERGE IV Network and anticipate developing consensus across the Network for the PRSs and GREs applied. The care of families will exploit the harmonization of the electronic health records between the adult and pediatric hospitals, which has been achieved with the Maternal and Infant Data Hub (MIDH) using the Observational Medical Outcomes Partnership (OMOP) common data model. For data quality control we will evaluate discrepancies between eMERGE IV genotyping and low read depth coverage (LRDC) genotypes (LRDC sequencing will be at CCHMC expense.) We will collect preferences and attitudes of our local AA community with respect to genomic results and return of results. We will develop health risk-reducing recommendations and return GREs with and without actionable PRSs to assess the influence of PRSs on the adherence to risk-mitigating recommendations. We will use SMART on FHIR (Substitutable Medical Applications, Reusable Technologies and Fast Healthcare Interoperability Resource) through the electronic health record (EHR)-integrated clinical decision support (CDS)-Hooks framework to provide CDS to both the adult and pediatric EHR systems. We will periodically revise PRSs and GREs and return changes when indicated. CCHMC will provide LRDC sequencing from >17,000 DNA AA samples from children in the CCHMC biobank and ≥50,000 subjects in total for genotype generation and mitochondrial DNA variant analysis. Federated geocoding will be available to all eMERGE IV sites from CCHMC. To disseminate genomic practice within CCHMC, across the Network, and in general, CCHMC will provide services to advance PRSs and GREs for specific conditions, starting with acute lymphoblastic leukemia, migraine headache, and suicide. In sum, CCHMC presents an aggressive program use genomic medicine to advance toward better health outcomes focused on underserved AA dyads of neonates and mothers with their families.