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）是致盲的主要原因。这种疾病对非裔美国人的影响尤为严重，他们患此病的风险比同龄的白种人高4到5倍。除了患病率高外，非洲裔美国人青光眼致盲的风险是白种人的10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未充分研究的非裔美国人人群中负责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，包括补体因子H作为年龄相关性黄斑变性最强遗传危险因素的鉴定。这些方法通常利用成千上万的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洲裔美国人的青光眼，因为成本极高，而且因为收集必要数据集的困难：历史研究的滥用使许多潜在的非洲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新的全基因组关联技术来解决，这种技术称为混合映射。混合定位是一种全基因组关联技术，它利用了混合人群（如非洲裔美国人）独特的遗传结构。它最近被用来成功地绘制多发性硬化症和前列腺癌的基因图谱。混合作图比其他形式的全基因组关联的每个样品便宜4-5倍，因为它需要更少的标记，同时保持检测疾病相关易感性变异的类似能力。此外，这项技术只使用非裔美国人病例，不需要匹配对照，因此可以进行高功率的初始基因组扫描。将在西非加纳收集的大型POAG病例/对照数据集中对基因组扫描进行随访。非洲裔美国人青光眼易感基因的鉴定可以改善这一严重影响和研究不足的人群的治疗方法。青光眼在非裔美国人中尤为常见和严重。我们正在使用一种新的基因技术来寻找导致这一人群青光眼的基因。找到这样的基因可以通过更好的治疗方法来预防失明。

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.