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.

项目总结 青光眼由于视神经损伤而导致视力丧失，如果未被发现或 未经治疗。最常见的青光眼形式是原发性开角型青光眼(POAG)。而青光眼 影响到所有种族，非洲裔人受到的影响不成比例；研究表明，非洲裔美国人 (AA)患这种疾病的可能性大约是高加索美国人的四到五倍。青光眼是 非洲裔美国人不可逆转失明的首要原因，以及 都是美国人。 对POAG的病因缺乏了解阻碍了我们早期识别和治疗它的能力 它的发展。基因在POAG发病机制中的作用的证据是确凿的。自.以来 POAG倾向于家族遗传，确定疾病的遗传基础对于疾病的发展至关重要 早期干预的有效疗法。 而针对高加索人的青光眼全基因组关联研究(GWAS)已经完成 在人群中，来自其他研究的证据表明，非洲人青光眼特异基因的GWAs- 美国人群将为这一人群和青光眼患者带来独特而重要的发现 将军。更好地理解疾病阶段、变化率、血统、 以及正在进行的非洲人下降和青光眼研究中追踪的其他重要风险因素(ADAGES) 将使我们能够评估遗传学、视力丧失和结构损伤之间的关系 一群人。 这项新研究的科学计划详细介绍了约2000名非裔美国人中的青光眼 新受试者的表型鉴定，从新的和已建立的表型鉴定中获取样本 研究对象为存储库，建立数据协调中心，并建立全基因组关联 学习。现有学科和新学科的招募、注册和表型鉴定都在四点进行。 临床中心，加州大学(UCSD)，纽约大学眼耳医院 亚特兰大地区的一家私人诊所，以及阿拉巴马大学伯明翰分校。加州大学洛杉矶分校也是 以Robert N.Weinreb为负责人的数据协调中心和存储库的位置 调查员。CSMC将利用一个由大约250万个单核苷酸多态组成的GWAS小组进行基因分型 (SNPs)加上一组约300,000个SNPs，使用Illumina Omni2.5 Plus外显子组平台 导演杰罗姆·罗特和肯特·泰勒。CSMC还将提供3435个对照的GwA和EXOME数据。 与青光眼相关的GWASNPs和外显子SNPs和数据的比较和确认将是 与宾夕法尼亚大学的类似青光眼研究进行了比较和证实。