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导致视力丧失，如果不及时发现或治疗，这种损伤是不可逆转的。最常见的青光眼是原发性开角型青光眼（POAG）。虽然青光眼影响所有种族，但非洲人后裔受到的影响尤为严重；研究表明，非裔美国人（AAs）患这种疾病的可能性是白种人的四到五倍。青光眼是非洲裔美国人不可逆转失明的主要原因，也是所有美国人的第二大原因。缺乏对POAG病因的了解阻碍了我们在其发展早期识别和治疗它的能力。遗传在POAG发病机制中的作用已得到充分证实。由于POAG倾向于家族遗传，因此确定该疾病的遗传基础以开发有效的早期干预疗法至关重要。虽然对白种人青光眼的基因组全关联研究（GWAS）已经完成，但来自其他研究的证据表明，对非洲裔美国人青光眼特异性基因的基因组全关联研究将为该人群和一般青光眼产生独特而重要的发现。在正在进行的非洲裔和青光眼研究（ADAGES）中，更好地了解疾病阶段、变化率、祖先和其他重要危险因素之间的关系，将使我们能够评估这一高风险队列中遗传、视力丧失和结构损伤之间的关系。这项新研究的科学计划将重点放在约2000名非洲裔美国人的青光眼上，通过对新受试者进行详细的表型分析，从新的和已经建立的表型研究受试者中获取样本，建立一个数据协调中心，并进行全基因组关联研究。在四个临床中心，加利福尼亚大学（UCSD）、纽约眼耳医院、纽约医科大学（亚特兰大地区的一家私人诊所）和阿拉巴马大学伯明翰分校，招募、登记和分型既有受试者和新受试者。加州大学圣地亚哥分校也是数据协调中心和存储库的所在地，Robert N. Weinreb担任首席研究员。在Jerome Rotter和Kent Taylor的指导下，CSMC将使用约250万个单核苷酸多态性（snp）的GWAS面板和约30万个snp的外显子组，使用Illumina Omni2.5 +外显子组平台进行基因分型。CSMC还将提供3435组对照的GWAS和外显子组数据。GWAS和外显子组snp以及青光眼相关数据的比较和确认将与宾夕法尼亚大学类似的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.