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。这种疾病不成比例地影响非洲裔美国人，他们的患病风险比年龄匹配的白人高出四到五倍。除了其高患病率之外，非裔美国人青光眼致盲的风险是高加索人的10倍以上，使其成为非裔美国人致盲的主要原因。这项研究的目的是确定共同的基因，是负责特发性原发性开角型青光眼在研究不足的非洲裔美国人的人口。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，包括将补体因子H鉴定为年龄相关性黄斑变性的最强遗传风险因子。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青光眼的非裔美国人，因为成本极高，因为难以组装必要的数据集：历史研究滥用，使许多潜在的非裔美国人控制不愿意参与医学研究。这两个困难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，它利用了混合人群（如非洲裔美国人）的独特遗传结构。它最近已被用于成功地绘制多发性硬化症和前列腺癌的基因图谱。混合物作图每个样品比其他形式的全基因组关联便宜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体的相似能力。此外，该技术仅使用非裔美国人病例，不需要匹配对照，因此能够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/对照数据集中进行基因组扫描的随访。在非裔美国人中鉴定青光眼易感基因可能会导致改善这种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其常见和严重。我们正在使用一种新的遗传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地治疗这种疾病来预防失明。

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.