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

描述（由申请人提供）：青光眼由于视神经损伤而导致视力丧失，如果未检测到或未治疗，则不可逆。青光眼最常见的形式是原发性开角型青光眼（POAG）。虽然青光眼影响所有种族，但非洲裔人受到的影响不成比例;研究表明，非洲裔美国人（AAs）患青光眼的可能性是白人美国人的四到五倍。青光眼是非洲裔美国人不可逆失明的主要原因，也是所有美国人的第二大原因。 对原发性开角型青光眼病因学的认识不足阻碍了我们在其发展早期识别和治疗它的能力。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。由于POAG倾向于在家庭中运行，因此确定疾病的遗传基础以开发早期干预的有效疗法至关重要。 虽然青光眼的全基因组关联研究（GWAS）已经在高加索人群中完成，但来自其他研究的证据表明，对非洲裔美国人人群的青光眼特异性基因的GWAS将为该人群和一般青光眼产生独特而重要的发现。更好地了解疾病阶段，变化率，血统和正在进行的非洲血统和青光眼研究（ADAGES）中跟踪的其他重要风险因素之间的关系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。 这项新研究的科学计划通过对新受试者进行详细的表型分析，从新的和以前建立的表型研究受试者中采集样本用于储存库，建立数据协调中心，以及全基因组关联研究，重点关注约2000名非洲裔美国人的青光眼。已建立和新受试者的招募、入组和表型分型发生在四个临床中心，即加州大学（UCSD）、纽约眼耳医院、纽约医学大学（亚特兰大地区的私人诊所）和伯明翰的亚拉巴马大学。加州大学圣地亚哥分校也是数据协调中心和存储库的位置与罗伯特N。Weinreb担任首席研究员。CSMC将在杰罗姆罗特和肯特泰勒的指导下，使用Illumina Omni2.5 plus外显子组平台，使用约250万个单核苷酸多态性（SNP）的GWAS面板加上约300，000个SNP的外显子组进行基因分型。CSMC还将提供3435对照的GWAS和外显子组数据。GWAS和外显子组SNP的比较和确认以及青光眼相关数据将与宾夕法尼亚大学的类似青光眼研究进行比较和确认。

DESCRIPTION (provided by applicant): 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.