xADAGES III: Contribution of genotype to glaucoma phenotype in African Americans

xADAGES III：基因型对非裔美国人青光眼表型的贡献

• 批准号: 8559980
• 负责人: Jerome I Rotter
• 金额: $ 157.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8559980
• 关键词: Affect; African; African American; Alabama; American; Area; Biometry; Blindness; California; Caucasians; Caucasoid Race; Clinical; Collaborations; Cornea; Custom; DNA; Data; Data Analyses; Data Coordinating Center; Data Set; Database Management Systems; Databases; Detection; Development; Diagnosis; Diagnostic; Disease; Drug Targeting; Ear; Early Intervention; Enrollment; Ethnic group; Etiology; European; Evaluation Studies; Eye; Family; Functional disorder; Future; Genes; Genetic; Genome; Genotype; Glaucoma; Goals; Institutes; Large-Scale Sequencing; Lead; Linkage Disequilibrium; Location; Maps; Medical Genetics; Medical center; Medicine; Meta-Analysis; Methods; Minority; New York; Optic Nerve; Pathogenesis; Pathway interactions; Patients; Pattern; Pennsylvania; Persons; Phenotype; Physiologic Intraocular Pressure; Population; Primary Open Angle Glaucoma; Principal Investigator; Private Practice; Proxy; Quality Control; Race; Risk Factors; Running; Sampling; Severities; Single Nucleotide Polymorphism; Staging; Study Subject; Technology; Testing; Thick; Time; Universities; Variant; Visual; Visual Fields; Visual impairment; base; caucasian American; clinical research site; cohort; design; effective therapy; exome; genetic variant; genome wide association study; high risk; improved; innovation; predictive modeling; public health relevance; repository; trait

PROJECT SUMMARY Glaucoma results in vision loss due to damage of the optic nerve that is irreversible if undetected or untreated. The most common form of glaucoma is primary open angle glaucoma (POAG). While glaucoma affects all races, persons of African descent are disproportionately affected; studies show African Americans (AAs) are about four to five times more likely than Caucasian Americans to develop the disease. Glaucoma is the leading cause of irreversible blindness in Americans of African descent, and the second leading cause in all Americans. The lack of understanding about the etiology of POAG impedes our ability to identify and treat it early in its development. Evidence of genetic contribution in the pathogenesis of POAG is well established. Since POAG tends to run in families, it is critical to identify the genetic basis of the disease in order to develop effective therapies for early intervention. While genome wide association studies (GWAS) for glaucoma have been completed for Caucasian populations, evidence from other studies suggests that a GWAS of glaucoma specific genes to the African- American population will yield unique and important findings for both this population and for glaucoma in general. A better understanding of the relationship among the stage of disease, the rate of change, ancestry, and other important risk factors being tracked in the ongoing African Descent and Glaucoma Study (ADAGES) will allow us to evaluate the relationship between genetics, visual loss and structural damage in this high-risk cohort. The scientific plan for this new study focuses on glaucoma in ~2000 African-Americans by detailed phenotyping of new subjects, acquisition of samples from both new and established previously phenotyped study subjects for a repository, establishment of a data coordinating center, and genome wide association studies. The recruitment, enrollment, and phenotyping of both established and new subjects occurs at four clinical centers, University of California (UCSD), New York Eye and Ear Infirmary New York University of Medicine, a private practice in the Atlanta area, and the University of Alabama at Birmingham. UCSD is also the location for the Data Coordinating Center and the Repository with Robert N. Weinreb as Principal Investigator. CSMC will do the genotyping with a GWAS panel of ~2.5 million single nucleotide polymorphisms (SNPs) plus an exome set of ~300,000 SNPs using the Illumina Omni2.5 plus exome platform under the direction of Jerome Rotter and Kent Taylor. CSMC will also provide GWAS and exome data for 3435 controls. Comparison and confirmation of the GWAS and exome SNPs and data associated with glaucoma will be compared and confirmed with the University of Pennsylvania's similar glaucoma study.

项目摘要 青光眼导致视力损失是由于视神经的损害而导致的，如果未被发现或 未经处理。青光眼最常见的形式是原发性开角青光眼（POAG）。而青光眼 影响所有种族，非洲血统的人受到不成比例的影响；研究表明非裔美国人 （AAS）发展这种疾病的可能性是高加索美国人的四到五倍。青光眼是 非洲后裔美国人不可逆转的失明的主要原因，以及 所有美国人。 对POAG病因的缺乏理解阻碍了我们在早期识别和对待它的能力 它的发展。 POAG发病机理中遗传贡献的证据已得到很好的确定。自从 POAG倾向于在家庭中运行，至关重要的是要确定疾病的遗传基础以发展 早期干预的有效疗法。 而基因组广泛的结合研究（GWAS）已完成高加索的青光眼研究 人群，其他研究的证据表明，非洲 - 非洲的青光眼特异性基因的GWA 美国人口将为该人群和青光眼产生独特而重要的发现 一般的。更好地了解疾病阶段之间的关系，变化率，祖先， 以及正在进行的非洲血统和青光眼研究（ADAGES）中追踪的其他重要危险因素 将使我们能够评估这种高风险的遗传学，视觉丧失和结构损害之间的关系 队列。 这项新研究的科学计划侧重于2000年的非裔美国人的青光眼 新主题的表型，从新的和已建立的表型中获取样品 存储库的研究对象，建立数据协调中心和基因组广泛的关联 研究。已建立和新主题的招募，入学和表型发生在四个 加利福尼亚大学临床中心（UCSD），纽约眼和耳朵医务室纽约大学 医学，亚特兰大地区的私人执业，以及伯明翰的阿拉巴马大学。 UCSD也是 与Robert N. Weinreb担任数据协调中心和存储库的位置 研究者。 CSMC将使用约250万个单核苷酸多态性的GWAS面板进行基因分型 （SNP）加上一组约300,000个SNP，使用Illumina omni2.5加上外来平台 杰罗姆·鹿特（Jerome Rotter）和肯特·泰勒（Kent Taylor）的方向。 CSMC还将为3435个控件提供GWAS和外部数据。 GWAS和Exome SNP的比较和确认以及与青光眼相关的数据将是 与宾夕法尼亚大学类似的青光眼研究进行了比较并证实。