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

描述(申请人提供)：青光眼导致视力丧失，由于视神经损伤，如果没有发现或治疗是不可逆的。最常见的青光眼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，非洲裔美国人患青光眼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，也是所有美国人的第二大原因。对POAG的病因缺乏了解阻碍了我们在其发展的早期识别和治疗它的能力。基因在POAG发病机制中的作用的证据是确凿的。由于POAG倾向于在家族中发生，因此确定疾病的遗传基础以开发有效的治疗方法进行早期干预是至关重要的。虽然针对高加索人群的青光眼全基因组关联研究(GWAS)已经完成，但来自其他研究的证据表明，对非裔美国人的青光眼特异基因进行全基因组关联研究将对这一人群和整个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人下降和青光眼研究(ADAGES)中追踪的其他重要风险因素之间的关系，将使我们能够在这一高危队列中评估遗传、视力丧失和结构损伤之间的关系。这项新研究的科学计划集中在约2000名非裔美国人中的青光眼，方法是对新的受试者进行详细的表型鉴定，从新的和先前建立的表型研究对象中获取样本作为资料库，建立数据协调中心，以及全基因组关联研究。现有受试者和新受试者的招募、注册和表型鉴定都在四个临床中心进行，这四个中心分别是加州大学(UCSD)、纽约眼耳医院、亚特兰大地区的一家私人诊所纽约医科大学和阿拉巴马大学伯明翰分校。加州大学圣迭戈分校也是数据协调中心和存储库的所在地，罗伯特·N·温雷布担任首席调查员。CSMC将在Jerome Rotter和Kent Taylor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(SNPs)和一个约30万个单核苷酸多态(SNPs)的外显子组进行基因分型。CSMC还将提供3435个对照的GwA和EXOME数据。与青光眼相关的GWAS和外显子SNPs和数据的比较和确认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.