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

xADAGES III：基因型对非裔美国人青光眼表型的贡献

基本信息

批准号：
8559980
负责人：
Jerome I Rotter
金额：
$ 157.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8559980
关键词：
Affect African African American Alabama American Area Biometry Blindness California Caucasians Caucasoid Race Clinical Collaborations Cornea Custom DNA Data Data Analyses Data Coordinating Center Data Set Database Management Systems Databases Detection Development Diagnosis Diagnostic Disease Drug Targeting Ear Early Intervention Enrollment Ethnic group Etiology European Evaluation Studies Eye Family Functional disorder Future Genes Genetic Genome Genotype Glaucoma Goals Institutes Large-Scale Sequencing Lead Linkage Disequilibrium Location Maps Medical Genetics Medical center Medicine Meta-Analysis Methods Minority New York Optic Nerve Pathogenesis Pathway interactions Patients Pattern Pennsylvania Persons Phenotype Physiologic Intraocular Pressure Population Primary Open Angle Glaucoma Principal Investigator Private Practice Proxy Quality Control Race Risk Factors Running Sampling Severities Single Nucleotide Polymorphism Staging Study Subject Technology Testing Thick Time Universities Variant Visual Visual Fields Visual impairment base caucasian American clinical research site cohort design effective therapy exome genetic variant genome wide association study high risk improved innovation predictive modeling public health relevance repository trait

项目摘要

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.

项目概要青光眼由于视神经损伤而导致视力丧失，如果未发现或未发现，这种损伤是不可逆转的未经治疗。最常见的青光眼形式是原发性开角型青光眼（POAG）。而青光眼影响所有种族，其中非洲人后裔受到的影响尤为严重；研究表明非裔美国人（AA）患这种疾病的可能性是白人美国人的四到五倍。青光眼是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。对 POAG 病因缺乏了解阻碍了我们早期识别和治疗的能力它的发展。遗传因素在 POAG 发病机制中的作用的证据已得到充分证实。自从 POAG 往往有家族遗传倾向，确定该疾病的遗传基础对于发展至关重要早期干预的有效疗法。虽然白种人青光眼的全基因组关联研究 (GWAS) 已经完成其他研究的证据表明，青光眼特异性基因的 GWAS 与非洲人美国人口将为该人群和青光眼带来独特而重要的发现一般的。更好地了解疾病阶段、变化率、祖先、以及正在进行的非洲人后裔和青光眼研究 (ADAGES) 中正在追踪的其他重要风险因素将使我们能够评估这种高风险中遗传、视力丧失和结构损伤之间的关系队列。这项新研究的科学计划重点关注约 2000 名非洲裔美国人的青光眼，详细研究新受试者的表型分析，从新的和已建立的先前表型中采集样本存储库的研究主题、数据协调中心的建立以及全基因组关联研究。已建立的和新的受试者的招募、注册和表型分析发生在下午四点加州大学 (UCSD) 临床中心、纽约眼耳医院纽约大学医学、亚特兰大地区的私人诊所和阿拉巴马大学伯明翰分校。加州大学圣地亚哥分校也是由 Robert N. Weinreb 担任负责人的数据协调中心和存储库的位置研究者。华润上华将使用约 250 万个单核苷酸多态性的 GWAS 面板进行基因分型 (SNP) 加上约 300,000 个 SNP 的外显子组，使用 Illumina Omni2.5 plus 外显子组平台在杰罗姆·罗特和肯特·泰勒执导。华润上华还将提供 3435 对照的 GWAS 和外显子组数据。与青光眼相关的 GWAS 和外显子组 SNP 以及数据的比较和确认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。