The NEIGHBORHOOD: POAG Heritable Overall Operational Database

NEIGHBORHOOD：POAG 可遗传整体运营数据库

• 批准号: 8265099
• 负责人: Janey L Wiggs
• 金额: $ 45.09万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265099
• 关键词: Affect; Architecture; Blindness; Clinic; Clinical; Collaborations; Collection; Data; Data Set; Databases; Development; Environmental Exposure; Etiology; Future; Genes; Genetic; Genetic Determinism; Genetic Variation; Genome; Genotype; Glaucoma; Goals; Health; Health Professional; Heritability; Housing; Human Genetics; Individual; Investigation; Iowa; Logistics; Maintenance; Meta-Analysis; Molecular; Neuropathy; Nurses' Health Study; Ocular Hypertension; Optic Nerve; Outcome; Participant; Pathogenesis; Patients; Phenotype; Physiologic Intraocular Pressure; Prevention strategy; Primary Open Angle Glaucoma; Primary Prevention; Public Health; Refractive Errors; Research; Research Personnel; Resources; Risk Factors; Sample Size; Sampling; Screening procedure; Structure; Subgroup; Techniques; Universities; Venous Thrombosis; Visual Fields; Woman; base; case control; data mining; database of Genotypes and Phenotypes; endophenotype; follow-up; gene environment interaction; genetic resource; genome wide association study; genome-wide; hypertension treatment; insight; member; novel; optic nerve disorder; trait

DESCRIPTION (provided by applicant): Primary open angle glaucoma (POAG) is a significant cause of blindness worldwide. The etiology of POAG is poorly understood and primary prevention is not possible. Current treatments can slow but do not cure this progressive neuropathy. The overall goal of our research is to elucidate the pathogenesis of primary open-angle glaucoma (POAG) making it possible to implement effective screening and prevention strategies and to develop novel therapies. While POAG has a significant heritability, recent genome-wide association studies using moderate sample sizes have only identified a few POAG-related genes with modest effect sizes. These results suggest that large datasets with well-defined phenotypes are needed to fully delineate the genetic architecture of POAG. This proposal will efficiently use existing datasets to create a large sample useful for investigation o genetic determinants of POAG, with a primary focus of identifying genes contributing to the POAG-related quantitative endophenotype, cup-to-disc ratio (CDR). Emerging data suggests that CDR, even when subjectively ascertained, is an important outcome providing valuable insights into the pathogenesis of POAG. Previously we formed two collaborative consortia contributing 3,517 POAG cases and 3,631 controls for GWA studies, the NEIGHBOR consortium (NEI Glaucoma Human genetic collaboration) and the GLAUGEN study (Glaucoma Genetics). The immediate goals of this proposal are: 1) expand the NEIGHBOR and GLAUGEN consortia to create the NEIGHBORHOOD (NEIGHBOR Heritable Overall Operational Database) consortium and database, which will include harmonized genotype and phenotype data for a total of 4,652 POAG cases, 16,909 subjects with CDR and 42,486 controls~ and, 2) use this enhanced dataset to perform meta-analyses to identify novel genes influencing CDR, as well as genes that contribute to POAG. Additionally, this proposal will form the basis of future studies of other POAG related traits and gene-gene and gene-environment interactions for CDR and POAG. PUBLIC HEALTH RELEVANCE: Primary open angle glaucoma (POAG) causes permanent loss of vision and is a condition of public health significance worldwide, affecting millions of people. The etiology of POAG is poorly understood and effective means of primary prevention and curative therapies are not available. In this proposal, our collaborative consortium will develop an operational database housing phenotype and genotype information for over 4600 POAG cases, 16,000 individuals with data for the heritable POAG endophenotype cup-to-disc ratio (CDR), and 42,000 controls that can be used to identify risk factors for POAG with the ultimate goal of elucidating the molecular pathogenesis of POAG making it possible to implement effective screening and prevention strategies and to develop novel therapies.

描述（由申请人提供）：主要的开角青光眼（POAG）是全球失明的重要原因。 POAG的病因鲜为人知，而主要的预防是不可能的。 当前的治疗可能会放慢，但不能治愈这种进行性神经病。 我们研究的总体目的是阐明主要的开态青光眼（POAG）的发病机理，使实施有效的筛查和预防策略并开发新疗法成为可能。 尽管POAG具有显着的遗传力，但使用中等样本量的最新基因组关联研究仅确定了一些与POAG相关的基因，具有适度的效应量。 这些结果表明，需要具有明确定义的表型的大型数据集充分描述POAG的遗传结构。 该提案将有效地使用现有数据集创建用于研究POAG的遗传决定因素有用的大型样本，其主要重点是鉴定有助于POAG相关的定量内表型的基因，杯赛与二轴比率（CDR）。 新兴数据表明，即使在主观上确定的情况下，CDR也是重要的结果，为POAG的发病机理提供了宝贵的见解。 以前，我们形成了两个合作联盟，其中贡献了3,517例POAG病例和3,631例GWA研究，邻居联盟（NEI青光眼人类遗传协作）和Glaugen研究（青光眼遗传学）。 该提案的直接目标是：1）扩大邻居和夸张的财团，以创建社区（邻居可遗传的总体操作数据库）财团和数据库，其中包括统一的基因型和表型数据，共4,652个POAG案例，共16,909名受试者，与CDR和42,486 Controls一起使用，并识别该数据，并识别2,486个基因，2）影响CDR以及有助于POAG的基因。 此外，该提案将构成其他与POAG相关性状以及CDR和POAG的基因环境相互作用的未来研究的基础。 公共卫生相关性：主要的开角青光眼（POAG）会导致永久视力丧失，并且是全球公共卫生意义的状况，影响了数百万的人。 POAG的病因知之甚少，有效的原发性预防手段和治疗疗法没有可用。 在这项提议中，我们的协作财团将开发一个可用于4600多个POAG案件的操作数据库外壳表型和基因型信息，16,000名具有可遗传性POAG内类型型杯式杯式比率（CDR）的数据的人，以及42,000个控制，以及可用于识别POAG的最终策略和POAG的poag protitive and poag pro andive poag and poag的最终因素的控制因素，以使其有效地造成了POAG的造成量的poag，并可以使POAG造型构成POAG的最终功能，以使其有效地构成POAG的造型，并具有poag的范围。开发新颖的疗法。