The NEIGHBORHOOD: POAG Heritable Overall Operational Database

NEIGHBORHOOD：POAG 可遗传整体运营数据库

• 批准号: 8728250
• 负责人: Janey L Wiggs
• 金额: $ 39.45万
• 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/8728250
• 关键词: Affect; Architecture; Blindness; Clinic; Clinical; Collaborations; Collection; Data; Data Set; Databases; Development; Environmental Exposure; Etiology; Future; Genes; Genetic; Genetic Determinism; 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; 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; genetic variant; genome wide association study; genome-wide; hypertension treatment; insight; member; novel; optic nerve disorder; screening; 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.

描述（由申请人提供）：原发性开角型青光眼（POAG）是全世界失明的重要原因。 POAG 的病因尚不清楚，一级预防也是不可能的。 目前的治疗可以减缓但不能治愈这种进行性神经病。 我们研究的总体目标是阐明原发性开角型青光眼（POAG）的发病机制，使实施有效的筛查和预防策略以及开发新疗法成为可能。 虽然 POAG 具有显着的遗传力，但最近使用中等样本量的全基因组关联研究仅发现了一些效应大小适中的 POAG 相关基因。 这些结果表明，需要具有明确表型的大型数据集来充分描绘 POAG 的遗传结构。 该提案将有效地利用现有数据集创建一个大样本，用于研究 POAG 的遗传决定因素，主要重点是识别有助于 POAG 相关定量内表型、杯盘比 (CDR) 的基因。 新出现的数据表明，即使是主观确定的，CDR 也是一个重要的结果，为了解 POAG 的发病机制提供了宝贵的见解。 此前，我们成立了两个合作联盟，即 NEIGHBOR 联盟（NEI 青光眼人类遗传合作）和 GLAUGEN 研究（青光眼遗传学），为 GWA 研究贡献了 3,517 例 POAG 病例和 3,631 例对照。 该提案的直接目标是：1) 扩展 NEIGHBOR 和 GLAUGEN 联盟，创建 NEIGHBORHOOD（NEIGHBOR 可遗传整体操作数据库）联盟和数据库，其中将包括总共 4,652 个 POAG 病例、16,909 个具有 CDR 的受试者和 42,486 个对照的统一基因型和表型数据~以及，2）使用此增强的数据集来执行荟萃分析以确定新基因 影响 CDR 以及导致 POAG 的基因。 此外，该提案将构成未来研究其他 POAG 相关性状以及 CDR 和 POAG 的基因-基因和基因-环境相互作用的基础。