Enriching medical phenotypes and environmental traits in the large DS360 Down syndrome cohort

总结 唐氏综合征（DS）导致结构性出生缺陷和健康状况的重大风险， 严重程度有很大的变化。全基因组测序（WGS） 1700唐氏综合征（DS）先证者通过三个服务奖。在这份R 03中，我们请求资金， 该已建立的DS-WGS队列的可用表型数据（KF-X 01-DS-CHD dbGaP登录号 phs 002330），并将这些数据与其他资源协调一致，以确保这一首创的影响最大化 基因型/表型投资DS研究。这些样本由四个研究小组提供， 埃默里大学的DS 360研究贡献了最大的队列。对于大多数参与者，表型评估是 仅在一个时间点完成，尽管我们确实通过采访提供了大量信息 先证者母亲的出生时间。我们提出两个目标，以扩大，丰富和协调这第一- 为DS研究社区提供同类WGS资源。 我们将扩大埃默里大学DS 360项目参与者的医学表型数据， 服务器租用-美国服务租用如果我们有WGS数据，我们将重新联系参与者，以完成更新的病史 问卷这些数据将作为后续病历收集的指南。护理人员报告 数据可能是唯一的信息来源;因此，这些报告对于识别出生缺陷的存在至关重要 沿着迟发性疾病。如果护理人员在病史中指出了医疗状况， 调查问卷，我们将尝试从这些提供者获得医疗记录。这些医疗记录将 抽象成一个标准化的医疗记录汇总表。 我们将对DS 360参与者的现有表型和母体环境变量进行管理， 谁WGS是可用的，并映射诊断本体术语，以扩大潜在的识别DS- 相关的遗传和环境风险因素。我们从访谈中获得了大量的问卷数据 与DS先证者的母亲进行。我们将与Kids First的数据协调中心合作， INCLUDE协调这些综合数据，并将其映射到标准本体术语上，以促进 在Kids First大型队列中进行交叉疾病分析，并允许在 DS研究社区 拟定的新数据收集，沿着我们现有的数据，包括临床和环境数据 变量，将被策划，协调和共享。这一扩展的数据将加强对DS的研究， 促进跨疾病分析。

Summary Down syndrome (DS) leads to a significant risk for structural birth defects and health conditions, all presenting with substantial variability in severity. We have obtained whole genome sequencing (WGS) on approximately 1700 probands with Down syndrome (DS) via three service awards. In this R03, we request funds to enrich the available phenotype data on this established DS-WGS cohort (KF-X01-DS-CHD dbGaP accession number phs002330) and harmonize these data with other resources to ensure maximum impact of this first-of-its kind genotype/phenotype investment in DS research. These samples were contributed by four research groups, with Emory’s DS360 study contributing the largest cohort. For most participants, phenotype evaluation was done at one time point only, although we do have substantial information provided by our interviews around the time of birth with mothers of the probands. We propose two aims to expand, enrich and harmonize this first-of- its-kind WGS resource for the DS research community. We will expand medical phenotyping data on participants from Emory’s DS360 program on whom WGS is available. We will recontact participants where we have WGS data to complete an updated medical history questionnaire. These data will be used as a guide for subsequent medical record collection. Caregiver report data may be the sole source of information; thus, these reports are vital to identify presence of birth defects along with later-onset disorders. Where caregivers have indicated medical conditions in the medical history questionnaire, we will attempt to obtain medical records from those providers. These medical records will be abstracted into a standardized medical record summary form. We will curate existing phenotype and maternal environmental variables on participants in DS360 on whom WGS is available and map diagnoses to ontology terms to expand potential identification of DS- associated genetic and environmental risk factors. We have extensive questionnaire data from interviews conducted with mothers of probands with DS. We will work with the data coordinating centers of Kids First and INCLUDE to harmonize these comprehensive data and map them onto standard ontology terms to promote cross-disease analyses in the Kids First large set of cohorts and to allow new genotype/phenotype studies in the DS research community. The proposed new data collection, along with our existing data that include clinical and environmental variables, will be curated, harmonized and shared. This expanded data will enhance research on DS as well as promote cross-disease analyses.