Enhanced Data from Orofacial Cleft Trios to Strengthen the Gabriella Miller Kids First (GMKF) Discovery Goals

口面裂三重奏的增强数据可强化 Gabriella Miller Kids First (GMKF) 发现目标

• 批准号: 10599333
• 负责人: Mary L. Marazita
• 金额: $ 15.58万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599333
• 关键词: African; Anatomy; Area; Asian; Behavior Therapy; Biology; Child; Childhood; Classification; Cleft Lip; Clinical Medicine; Clinical Research; Colombian; Common Data Element; Communities; Complex; Computer Analysis; Computers; Congenital Abnormality; Consultations; Data; Data Element; Data Set; Dental; Disease; Economics; Equipment and supply inventories; Ethnic Origin; Etiology; European; Face; Filipino; Genetic; Genetic Variation; Genome; Genotype; Goals; Grant; Human; Individual; Infant Mortality; Information Retrieval; Intervention; Knowledge; Latin American; Life; Link; Live Birth; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical; Medical History; National Institute of Dental and Craniofacial Research; Nutritional; Ontology; Operative Surgical Procedures; Palate; Phenotype; Population; Pregnancy Histories; Public Health; Rare Diseases; Readability; Recording of previous events; Research; SNP array; Semantics; Speech; Standardization; Structural Congenital Anomalies; Structure; Treatment Cost; United States National Institutes of Health; Vocabulary; bioinformatics resource; biomedical ontology; clinical application; computable phenotypes; data harmonization; data resource; database of Genotypes and Phenotypes; feeding; genome sequencing; high risk; human disease; improved; mortality; orofacial cleft; phenotypic data; proband; programs; sex; whole genome

ABSTRACT Nonsyndromic orofacial clefts (OFCs) of the lip (CL), palate (CP), or both (CLP) occur in about 1/700 live births worldwide, and thus comprise a significant proportion of human structural birth defects. OFCs require surgical, nutritional, dental, speech, medical, and behavioral interventions, imposing substantial public health, economic, and personal burdens. On average a child with an OFC initially faces feeding difficulties, then undergoes intensive medical, dental, and speech interventions, leading to an estimated total lifetime treatment cost of about $200,000. Further, individuals born with an OFC have higher infant mortality, higher mortality rates at all other stages of life, and higher risk for other disorders (notably including some cancers). The etiology of OFCs is complex, clearly including a major genetic component with approximately 50 significantly associated loci identified to date. Thus we and others have received support from various NIH programs for SNP array genotyping, and also, notably, for whole-genome sequencing (WGS) primarily from the Gabriella Miller Kids First Initiative (GMKF). To date, we have received WGS through five separate GMKF grants for a total of 1,486 OFC proband trios. The sequence data from these projects are shared through the GMKF Data Resource Center and the phenotype data through the GMKF Data Resource Center and (in xome cases) dbGaP. To date, the most critical phenotype data has been uploaded to dbGaP (e.g. sex, population/ethnicity, OFC type), but there is a wealth of other phenotypic data available from these studies (e.g. details on the OFC birth defect, pregnancy history, medical/surgical history, etc) that is not yet part of the available data for these projects. The goal of this project is to make additional semantically curated data elements from the OFC studies available to the research community through GMKF, in order to expand the scope and value of the data from the GMKF orofacial cleft trios and to facilitate cross GMKF-study analyses.

抽象的 约 1/700 的活产婴儿中会出现唇裂 (CL)、腭裂 (CP) 或两者 (CLP) 的非综合征性口面裂 (OFC) 在世界范围内，因此构成了人类结构性出生缺陷的很大一部分。 OFC 需要手术， 营养、牙科、言语、医疗和行为干预，对公共卫生、经济、 和个人负担。平均而言，患有 OFC 的儿童最初会面临喂养困难，然后会经历 密集的医疗、牙科和言语干预，预计一生总治疗费用为 约20万美元。此外，出生时患有 OFC 的人婴儿死亡率更高，死亡率更高 生命的其他阶段，以及其他疾病（特别是某些癌症）的风险更高。 OFC 的病因很复杂，显然包括一个主要的遗传成分，大约有 50 迄今为止已确定的显着相关基因座。因此，我们和其他人得到了各个 NIH 的支持 用于 SNP 阵列基因分型的程序，尤其是用于全基因组测序 (WGS) 的程序，主要来自 加布里埃拉·米勒儿童第一倡议 (GMKF)。迄今为止，我们已通过五个独立的 GMKF 收到了 WGS 为总共 1,486 名 OFC 先证者三人组提供资助。这些项目的序列数据通过 GMKF 数据资源中心和表型数据通过 GMKF 数据资源中心和（在 xome 例）dbGaP。迄今为止，最关键的表型数据已上传到 dbGaP（例如性别、 人口/种族、OFC 类型），但这些研究还提供了大量其他表型数据 （例如，OFC 出生缺陷、怀孕史、医疗/手术史等详细信息）尚未属于 这些项目的可用数据。该项目的目标是制作额外的语义整理数据 OFC 研究的要素可通过 GMKF 提供给研究界，以便扩展 GMKF 口面裂三重奏数据的范围和价值，并促进跨 GMKF 研究 分析。