Admixture Mapping of Glaucoma Genes in African Americans

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不成比例，他们的患病风险是年龄匹配的高加索人的四到五倍。除了其高患病率外，非洲裔美国人患青光眼的风险是白人的10倍以上，使其成为非裔美国人失明的首要原因。这项研究的目的是在研究不足的非裔美国人群体中确定导致特发性原发性开角型青光眼的共同基因。全基因组关联(WGA)最近在复杂疾病的分析中取得了巨大的成功，包括发现补体因子H是老年性黄斑变性最强的遗传危险因素。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。这些方法没有应用于非裔美国人的青光眼，因为成本极高，而且很难收集必要的数据集：历史研究滥用使许多潜在的非裔美国人不愿参与医学研究。这两个困难都可以通过使用一种名为混合作图的新的全基因组关联技术来解决。混合作图是一种全基因组关联技术，它利用了非洲裔美国人等混合群体的独特遗传结构。它最近被成功地用于绘制多发性硬化症和前列腺癌的基因图谱。与其他形式的全基因组关联相比，混合作图每个样本的成本低4-5倍，因为它需要的标记要少得多，同时保持了检测疾病相关易感变异的类似能力。此外，这项技术只使用非裔美国人病例，不需要匹配的对照，从而实现了高功率的初始基因组扫描。基因组扫描的后续行动将在西非加纳收集的POAG病例/对照大型数据集中进行。在非裔美国人中识别青光眼易感基因可能会改进这一严重受影响和研究不足的人群的治疗方法。与公共卫生相关的青光眼在非裔美国人中尤其常见和严重。我们正在使用一种新的基因技术在这个人群中寻找导致青光眼的基因。找到这样的基因可以通过导致更好的疾病治疗来预防失明。

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.