Polygenic Risk Scores for Healthier African American Families

更健康的非洲裔美国家庭的多基因风险评分

基本信息

批准号：
10207723
负责人：
Leah Claire Kottyan
金额：
$ 166.98万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10207723
关键词：
7 year old Acute Lymphocytic Leukemia Adherence Adolescent Psychiatry Adult African American Age Ancillary Study Asthma Atopic Dermatitis Attitude Birth Brothers Caring Child Child Care Child Health Childhood Classification Clinic Collection Communities Computerized Medical Record Consensus DNA DNA Repository DNA analysis Data Disease Electronic Health Record Electronic Medical Records and Genomics Network Enrollment Environmental Risk Factor Ethical Issues Faculty Family Family member Fast Healthcare Interoperability Resources Fathers Feeling suicidal Fetus Future Generations Genetic Risk Genetic Variation Genome Genomic medicine Genomics Genotype Goals Health Health Promotion Healthcare Hospitals Hypertension Individual Infant Infrastructure Intervention Investments Knowledge Letters Longevity Machine Learning Medical Methods Migraine Mitochondrial DNA Mothers National Human Genome Research Institute Newborn Infant Obesity Outcome Parents Pediatric Hospitals Perception Performance Phenotype Quality Control Randomized Recommendation Recording of previous events Records Risk Risk Estimate Risk Management Sampling Services Siblings Sister Site Suicide Sum System Technology Testing Update Variant Vision Woman Work biobank care providers clinical care clinical decision support cohort data hub data modeling data quality disease phenotype disorder prevention disorder risk genome wide association study high risk hypercholesterolemia improved malignant breast neoplasm minority subjects neonate polygenic risk score preference pregnant premature programs recruit risk mitigation success support tools tool

项目摘要

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.

项目摘要为了促进儿童的健康和护理，与 eMERGE II 和 III 一样，CCHMC 将在 eMERGE IV，针对怀孕或最近分娩的自我认定的非裔美国 (AA) 女性和 eMERGE IV 系列将是他们的孩子以及愿意的父亲和兄弟姐妹的首次尝试。一项新的 CCHMC 倡议，由母亲和婴儿组成的出生队列，名为“我的基因组和我”，辛辛那提（MGMC），旨在加深对告知健康和疾病风险的基因组学的理解，开始出生时并持续整个生命周期，在入组时随机进行基因分型，并返回我们的 eMERGE IV 项目将直接解决伦理问题。通过将结果返回给具有不同操作考虑的婴儿、兄弟姐妹和父母的家庭来筹集资金关于正在研究的特定表型，我们提名 eMERGE IV 作为位点特异性表型。哮喘、特应性皮炎、肥胖、高胆固醇血症、高血压、早产和乳腺癌。将利用已完成的工作来开发多基因风险评分（PRS）和基因组风险评估 (GRE) 除了 eMERGE IV 网络选择的其他 15 个条件外，还适用于这些条件，并预计为所应用的 PRS 和 GRE 制定整个网络共识。家庭护理将利用成人医院和儿科医院之间电子健康记录的统一通过观察性医疗结果合作伙伴关系与母婴数据中心 (MIDH) 合作实现 (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。基因分型和低读深度覆盖 (LRDC) 基因型（LRDC 测序费用由 CCHMC 承担。）我们将收集当地 AA 社区对基因组结果和回报的偏好和态度我们将制定降低健康风险的建议，并返回 GRE（无论是否可行）。我们将使用 SMART 来评估 PRS 对遵守风险缓解建议的影响。 FHIR（可替代医疗应用、可重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）-综合临床决策支持（CDS）-Hooks 为成人和儿童 EHR 系统提供 CDS 的框架我们将定期修订 PRS 和 GRE 和返回更改（如有需要）将提供超过 17,000 个 DNA AA 的 LRDC 测序。来自 CCHMC 生物库中儿童和总共 ≥50,000 名受试者的样本用于基因型生成和线粒体 DNA 变异分析将适用于 CCHMC 的所有 eMERGE IV 站点。为了在 CCHMC 内部、整个网络和一般情况下传播基因组实践，CCHMC 将提供针对特定病症（从急性淋巴细胞白血病、偏头痛开始）推进 PRS 和 GRE 的服务总之，CCHMC 提出了一项利用基因组医学来推进的积极计划。致力于获得更好的健康结果，重点关注服务不足的 AA 二人组，即新生儿和母亲及其家人。