The NEIGHBORHOOD: POAG Heritable Overall Operational Database

NEIGHBORHOOD：POAG 可遗传整体运营数据库

• 批准号: 8511668
• 负责人: Janey L Wiggs
• 金额: $ 38.11万
• 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/8511668
• 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; 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; 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）是全球范围内致盲的重要原因。原发性开角型青光眼的病因尚不清楚，无法进行一级预防。 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，使其有可能实施有效的筛查和预防策略，并开发新的治疗方法。 虽然POAG具有显著的遗传性，但最近使用中等样本量的全基因组关联研究仅确定了少数具有中等效应大小的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述POAG的遗传结构。 该建议将有效地利用现有的数据集来创建用于调查POAG遗传决定因素的大样本，其主要重点是鉴定有助于POAG相关定量内表型，杯盘比（CDR）的基因。 新出现的数据表明，CDR，即使是主观确定，是一个重要的成果，提供了宝贵的见解POAG的发病机制。 此前，我们成立了两个合作联盟，为GWA研究提供了3，517例POAG病例和3，631例对照，即NEIGHBOR联盟（NEI Glaucoma Human genetics collaboration）和GLAUGEN研究（Glaucoma Genetics）。 这项建议的近期目标是：1）扩大NEIGHBOR和GLAUGEN联盟，创建NEIGHBORHOOD（NEIGHBOR遗传总体操作数据库）联盟和数据库，其中将包括总计4，652例POAG病例、16，909例CDR受试者和42，486例对照的协调基因型和表型数据，2）使用该增强的数据集进行荟萃分析，以鉴定影响CDR的新基因，以及有助于POAG的基因。 此外，这一建议将成为未来研究其他POAG相关性状和CDR和POAG的基因-基因和基因-环境相互作用的基础。