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

项目摘要 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。青光眼最常见的形式是原发性开角型青光眼（POAG）。虽然青光眼 影响到所有种族，非洲裔人受到不成比例的影响;研究表明， (AAs)比白种美国人患上这种疾病的可能性高出四到五倍。青光眼是 非洲裔美国人不可逆转失明的主要原因， 都是美国人 对原发性开角型青光眼病因学的认识不足，阻碍了我们早期识别和治疗该病的能力。 它的发展。遗传因素在原发性开角型青光眼发病机制中的作用已得到充分证实。以来 POAG倾向于在家庭中运行，确定疾病的遗传基础对于发展POAG至关重要。 早期干预的有效疗法。 虽然已经完成了高加索人青光眼的全基因组关联研究（GWAS）， 人群中，来自其他研究的证据表明，青光眼特异性基因的GWAS对非洲人， 美国人口将产生独特的和重要的发现，这两个人口和青光眼， 将军更好地理解疾病阶段、变化率、祖先、 正在进行的非洲人后裔和青光眼研究（ADAGES）中跟踪的其他重要风险因素 将使我们能够评估遗传学之间的关系，视力丧失和结构损伤，在这个高风险的， 队列。 这项新研究的科学计划通过详细的方法关注2000名非洲裔美国人的青光眼。 新受试者的表型分析，从新的和已确定的先前表型分析的受试者中采集样本 研究主题为一个知识库，建立一个数据协调中心，和基因组范围内的关联 问题研究已建立和新受试者的招募、入组和表型分型发生在4 临床中心，加州大学（UCSD），纽约眼耳医院，纽约大学 医学，亚特兰大地区的一家私人诊所，以及伯明翰的亚拉巴马大学。UCSD也是 数据协调中心和存储库的位置与罗伯特N。Weinreb作为校长 调查员CSMC将使用约250万个单核苷酸多态性的GWAS组进行基因分型 使用Illumina Omni2.5 plus外显子组平台，在测序平台下，使用约300，000个SNP的外显子组集合， 方向是杰罗姆罗特和肯特泰勒。CSMC还将提供3435对照的GWAS和外显子组数据。 GWAS和外显子组SNP的比较和确认以及与青光眼相关的数据将在 与宾夕法尼亚大学的类似青光眼研究进行了比较和证实。

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.