Genes and Environment Initiative in Glaucoma

青光眼基因与环境倡议

• 批准号: 7514579
• 负责人: Louis Robert Pasquale
• 金额: $ 44.14万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7514579
• 关键词: Accounting; Admixture; African American; Alleles; Biochemical Pathway; Biotechnology; Blindness; Candidate Disease Gene; Case-Control Studies; Caucasians; Caucasoid Race; Clinic; Collection; Complex; Condition; Consensus; Data; Databases; Diet; Disease; Disease Association; Ear; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; European; Eye; Family; Follow-Up Studies; Future; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genome; Genotype; Glaucoma; Goals; Health; Health Professional; Individual; Lead; Life Style; Maps; Massachusetts; Nurses' Health Study; Pathogenesis; Pathology; Pathway interactions; Phase; Phenotype; Physiologic Intraocular Pressure; Population; Population Analysis; Population Study; Populations at Risk; Prevention strategy; Primary Open Angle Glaucoma; Primary Prevention; Process; Public Health; Questionnaires; Relative Risks; Reporting; Research; Research Personnel; Risk; Sampling; Scanning; Scientist; Single Nucleotide Polymorphism; Staging; Susceptibility Gene; Testing; Variant; Visual Fields; Work; age related; base; blind; case control; cohort; cost; density; gene environment interaction; gene interaction; genetic variant; genome wide association study; member; optic nerve disorder; pre-clinical; programs

DESCRIPTION (provided by applicant): Primary open-angle glaucoma (POAG) is an age-related, intraocular pressure (lOP)-dependent progressive optic neuropathy that ultimately leads to blindness. Permanent vision loss from POAG is a condition of public health significance. Current evidence suggests that POAG is a polygenetic disease modified by environmental influences. We hypothesize that the identification and characterization of POAG susceptibility genes via a genome-wide association study (GWAS) will reveal significant environmental determinants that influence the disease process, as well as a better understanding of how gene-environment and gene-gene interactions contribute to this complex disease. For this study we have formulated a case-control study population from three cohorts: the Nurses Health Study (NHS); Health Professionals Follow-up Study (HPFS); and Massachusetts Eye and Ear Infirmary (MEEI). The cohort consists of 1200 cases and 1200 controls with DMA. Members of the NHS and HPFS also have repeated environmental exposure data over a 16 to 24 year period. We will perform a single-stage GWAS and carry out the appropriate statistical analyses to find genetic markers with the strongest association with POAG. Our replication plan to confirm the top genetic markers will involve a comparable population of 1400 cases and 1400 controls, a significant subset of which will also have repeated environmental exposure data. As part of this study, we will submit data on a myriad of environmental exposures (from members of NHS and HPFS) that could modify genetic predisposition for POAG to a central data repository. These results will generate a valuable collection of genotype, phenotype and environment exposure data, allowing scientists to test numerous hypotheses regarding how genes and environment relate to incident POAG. This study is also a crucial first step toward a better understanding of the underlying pathology responsible for POAG and will lead to future proposals to examine the relevance of the significant variants found in the Caucasian population in an African American admixture study, perform fine mapping and re-sequencing of candidate genes in at-risk populations, and investigate gene-gene interactions in POAG. Discovery of the various combinations of gene and environment interactions involved in POAG could lead to genotype-specific primary prevention strategies for this disease.

描述（由申请人提供）：主要的开角式青光眼（POAG）是与年龄相关的眼内压（LOP）依赖性进行性视神经病变，最终导致失明。 POAG的永久视力丧失是具有公共卫生意义的条件。当前的证据表明，POAG是一种由环境影响改变的多基因疾病。我们假设通过全基因组关联研究（GWAS）对POAG易感基因的鉴定和表征将揭示影响疾病过程的重要环境决定因素，并更好地了解基因环境和基因基因相互作用如何有助于这种复杂的疾病。在这项研究中，我们已经制定了三个同龄人的病例对照研究人群：护士健康研究（NHS）；卫生专业人员后续研究（HPFS）；和马萨诸塞州的眼睛和耳朵医务室（MEEI）。该队列由1200例和1200例DMA组成。 NHS和HPF的成员在16至24年期间还重复了环境暴露数据。我们将执行单阶段的GWAS并进行适当的统计分析，以找到与POAG最强关联的遗传标记。我们确认最高遗传标记的复制计划将涉及1400例和1400例对照的可比人群，其中很大的子集也将具有反复的环境暴露数据。作为这项研究的一部分，我们将提交有关无数环境暴露（来自NHS和HPF的成员）的数据，这些数据可能会改变POAG的遗传易感性。这些结果将产生宝贵的基因型，表型和环境暴露数据，从而使科学家可以检验许多关于基因和环境与事件POAG如何相关的假设。这项研究也是朝着更好地理解负责POAG的基本病理的至关重要的第一步，并将导致未来的建议在非裔美国人混合研究中研究在高加索人群中发现的重要变异的相关性，进行精细的映射和重新绘制和重新对处于风险的人群中的候选基因，并研究基因与Gene-Gene互动。发现POAG中涉及的基因和环境相互作用的各种组合可能会导致该疾病基因型特异性的原发性预防策略。