Primary Open Angle African-American Glaucoma Genetics (POAAGG)

描述（由申请人提供）：青光眼是全球范围内导致不可逆失明的主要原因，影响着大约7000万人。到2000年，有220万美国人被诊断患有青光眼，到2020年，这一数字预计将达到340万。原发性开角型青光眼（POAG）是一种引起视力丧失的疾病，与视网膜神经细胞的进行性和不可逆变性有关。70岁及以上的亚裔POAG患病率为3%，白种人为6%，非洲裔为16%。POAG在非裔美国人（AAs）中出现几乎早10年，进展更快，使其成为该人群中不可逆转失明的主要原因。众所周知，遗传学在这种疾病中起作用，然而，POAG遗传学是复杂的，涉及许多危险因素。这一建议代表了第一个专门评估aa遗传风险因素的大型人群研究。为了检查AAs与POAG的危险因素，将进行全基因组关联研究（GWAS）。GWAS是一种在大量人群中检测遗传变异以确定是否有任何变异与某种疾病或性状相关的方法。拟议的GWAS将在17000个AAs、2000个POAG和15000个对照中生成这些变异的数据。这种实验方法将确定与AAs中POAG相关的基因，这些AAs不成比例地患有这种疾病的更严重形式。许多不同的临床特征与POAG有关，对这种诊断的临床决定因素的研究将与遗传数据相关。将利用与在其他人口中探索这一方法的其他机构的合作进一步加强数据集。除了GWAS外，还将专门检查负责编码蛋白质的DNA部分，因为异常蛋白质与疾病易感性、进展和严重程度有关。在其他人群中也发现了POAG的遗传危险因素。这些已知风险因素的相关性，以及从拟议的GWAS调查中出现的新风险因素，将对非洲裔美国人进行评估。原发性开角非裔美国人青光眼遗传学研究（POAAGG）的最终目标是促进对AA型开角青光眼进行合理、有针对性的筛查、诊断和最终的新治疗。

DESCRIPTION (provided by applicant): Glaucoma is the leading cause of irreversible blindness worldwide, affecting approximately 70 million people. By 2000, 2.2 million Americans had been diagnosed with glaucoma, and this number is estimated to reach 3.4 million by 2020. Primary open angle glaucoma (POAG) is a spectrum of disease causing vision loss which is associated with progressive and irreversible degeneration of nerve cells in the retina. The prevalence of POAG is 3% among those of Asian ancestry, 6% among Caucasians, and 16% among those of African ancestry age 70 and older. POAG appears almost 10 years earlier and progresses more quickly in African Americans (AAs), making it the leading cause of irreversible blindness in this population. Genetics are known to play a role in this disease~ however, POAG genetics are complex, and many risk factors are involved. This proposal represents the first large population study specifically evaluating AAs for genetic risk factors. In order to examine AAs for POAG risk factors, a genome wide association study (GWAS) will be performed. GWAS is a method that detects genetic variants in a large population to determine if any variants are associated with a disease or trait. The proposed GWAS will generate data on these variants in 17,000 AAs, 2,000 with POAG and 15,000 controls. This experimental approach will identify genes associated with POAG in AAs, who disproportionately suffer from more severe forms of this disease. Many different clinical traits are associated with POAG, and investigation of clinica determinants of this diagnosis will be correlated with genetic data. Collaborations with other institutions that have explored this approach in other populations will be used to further enhance the data set. In addition to the GWAS, the portions of DNA responsible for coding proteins will be specifically examined, since abnormal proteins are associated with disease susceptibility, progression, and severity. Genetic risk factors for POAG have been identified in other populations. The relevance of these known risk factors, along with new risk factors that emerge from the proposed GWAS investigation, will be evaluated for Americans of African ancestry. The ultimate goal of the Primary Open Angle African-American Glaucoma Genetics Study (POAAGG) is to facilitate the development of rational, targeted screening, diagnosis and eventually novel treatments for AA POAG.