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，如出现的II和III中，CCHMC将在出现IV，确定怀孕或最近提供的自我认同的非裔美国人（AA）妇女和他们的婴儿，以及愿意的父亲和兄弟姐妹。出现的IV集合将是首个努力一项新的CCHMC倡议，母亲和婴儿二元组的出生群体叫我的基因组和我，辛辛那提（MGMC），想一想了解为健康和疾病风险提供依据的基因组学的理解出生时并继续在整个生命周期中，二元组在入学时随机分配为基因分型，返回结果是新生儿或更晚的孩子。我们出现的IV项目将直接应对道德问题通过返回结果的结果培养，在婴儿，兄弟姐妹和父母中有不同考虑因素关于正在研究的特定表型。对于出现的IV，作为特定地点表型，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。我们将利用所完成的工作，以发展多基因风险评分（PRS）和基因组风险估计（GRE）除了出现的IV网络选择的15个条件外，还可以预期针对PRSS和GRE应用的网络共识。家庭的照顾将利用成人和儿科医院之间电子健康记录的协调使用观察性医学结果伙伴关系，使用母亲和婴儿数据中心（MIDH）实现（OMOP）通用数据模型。对于数据质量控制，我们将评估出现IV之间的差异基因分型和低读取深度覆盖范围（LRDC）基因型（LRDC测序将以CCHMC费用为费用。）我们将收集我们当地AA社区在基因组结果方面的偏好和出席结果。我们将开发降低健康风险建议，并在有或没有可行的情况下返回GRE PRS评估PRS对依从性降低风险建议的影响。我们将使用智能在FHIR上（可替代的医疗应用，可重复使用的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（CD）为成人和儿科EHR系统提供CD的框架。我们将定期修改PRS，并指示时GRE和返回更改。 CCHMC将提供> 17,000 DNA AA的LRDC测序 CCHMC生物库中儿童的样本，基因型产生总共≥50,000名受试者线粒体DNA变异分析。联合地理编码将用于CCHMC的所有出现的IV站点。为了在CCHMC，整个网络中传播基因组实践，通常，CCHMC将提供从急性淋巴细胞白血病开始的特定条件下推进PRS和GRE的服务，偏头痛头痛和自杀。总而言之，CCHMC提出了一种积极的计划，使用基因组医学来推进致力于更好的健康成果，集中于服务不足的新生儿和母亲与家人。