Admixture Mapping of Glaucoma Genes in African Americans

非裔美国人青光眼基因的混合图谱

基本信息

批准号：
7681031
负责人：
MICHAEL A HAUSER
金额：
$ 54.08万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7681031
关键词：
Address Admixture Affect Africa African African American Age Age related macular degeneration Alleles American Blindness Budgets Candidate Disease Gene Caring Caucasians Caucasoid Race Chromosome Mapping Clinical Collection Complement Factor H Complex DNA Data Data Set Disease Ethnic group European Eye First Degree Relative Frequencies Funding Genes Genetic Genetic Markers Genetic Structures Genetic Techniques Genome Genome Scan Genotype Ghana Glaucoma Goals Grant High Prevalence Human Genome Individual Lead Malignant neoplasm of prostate Maps Medical Research Methods Multiple Sclerosis Patients Population Population Control Predisposition Prevalence Primary Open Angle Glaucoma Research Research Personnel Risk Sampling Scanning Source Speed Susceptibility Gene Techniques Testing Time Universities Variant case control cost design follow-up gene discovery genetic risk factor high risk improved meetings outreach program prevent public health relevance sex success

项目摘要

DESCRIPTION (provided by applicant): Primary open angle glaucoma (POAG) is a leading cause of blindness. This disease disproportionately affects African Americans, who have a four- to five-fold higher risk of disease than age-matched Caucasians. In addition to its high prevalence, the risk of blindness from glaucoma in African Americans is more than 10 times greater than Caucasians, making it the leading cause of blindness in African Americans. The goal of this study is to identify common genes that are responsible for idiopathic Primary Open Angle Glaucoma in the understudied African American population. Whole genome association (WGA) has recently met with dramatic success in the analysis of complex diseases, including the identification of Complement Factor H as the strongest genetic risk factor for age- related macular degeneration. These methods typically utilize hundreds of thousands of genetic markers to conduct case-control association tests on genes across the entire human genome. These methods have not been applied to glaucoma in African Americans because of the extremely high cost, and because of the difficulty of assembling the necessary dataset: historical research abuses have made many potential African American controls reluctant to participate in medical research. Both of these difficulties can be addressed through the use of a new whole genome association technique call admixture mapping. Admixture mapping is a whole-genome association technique that takes advantage of the unique genetic structure of admixed populations such as African Americans. It has recently been used to successfully map genes for multiple sclerosis and prostate cancer. Admixture mapping is 4-5 times less expensive per sample than other forms of whole-genome association because it requires many fewer markers while retaining similar power to detect disease-associated susceptibility variants. Further, this technique uses only African American cases and does not require matching controls, thus enabling a highly powered initial genome scan. Follow-up to the genome scan will be performed in a large POAG case/control dataset collected in Ghana, West Africa. The identification of glaucoma susceptibility genes in African Americans could lead to improved treatment methods for this severely affected and understudied population. PUBLIC HEALTH RELEVANCE Glaucoma is especially common and severe in African Americans. We are using a new genetic technique to find genes that contribute to glaucoma in this population. Finding such genes could prevent blindness by leading to better treatments for the disease.

描述（由申请人提供）：原发性开角型青光眼（POAG）是导致失明的主要原因。这种疾病对非裔美国人的影响尤为严重，他们患病的风险是同龄白人的四到五倍。除了发病率高之外，非洲裔美国人因青光眼失明的风险比白人高出十倍以上，使其成为非洲裔美国人失明的主要原因。本研究的目的是确定在非裔美国人群体中导致特发性原发性开角型青光眼的常见基因。全基因组协会 (WGA) 最近在复杂疾病的分析方面取得了巨大成功，包括将补体因子 H 确定为年龄相关性黄斑变性的最强遗传风险因素。这些方法通常利用数十万个遗传标记对整个人类基因组的基因进行病例对照关联测试。这些方法尚未应用于非裔美国人的青光眼，因为成本极高，而且难以收集必要的数据集：历史研究滥用使得许多潜在的非裔美国人对照不愿意参与医学研究。这两个困难都可以通过使用一种新的全基因组关联技术（称为混合作图）来解决。混合作图是一种全基因组关联技术，利用混合人群（例如非裔美国人）的独特遗传结构。它最近已成功用于绘制多发性硬化症和前列腺癌的基因图谱。混合作图每个样本的成本比其他形式的全基因组关联便宜 4-5 倍，因为它需要的标记要少得多，同时保留相似的检测疾病相关易感性变异的能力。此外，该技术仅使用非裔美国人病例，不需要匹配控制，从而实现高功率的初始基因组扫描。基因组扫描的后续工作将在西非加纳收集的大型 POAG 病例/对照数据集中进行。非洲裔美国人青光眼易感基因的鉴定可能会改善这一受到严重影响且研究不足的人群的治疗方法。公共卫生相关性青光眼在非裔美国人中尤其常见且严重。我们正在使用一种新的遗传技术来寻找导致该人群青光眼的基因。找到这样的基因可以通过更好的治疗方法来预防失明。