Genetic Epidemiology of Age-Related Macular Degeneration in the Older Order Amish

描述（由申请人提供）：通过对病例对照队列进行遗传分析，在鉴定年龄相关性黄斑变性的基因方面取得了显着进展。 大多数识别都是通过询问常见变异来完成的。 我们将开始鉴定始祖人群阿米什人中的罕见变异，并使用整个外显子组芯片来评估年龄相关性黄斑变性与编码变异的关联。 我们将通过使用现代成像技术（OCT）进一步完善年龄相关性黄斑变性的表型，以可视化年龄相关性黄斑变性的早期解剖学迹象。 我们假设存在与特定基因型相关的内表型，可用于确定年龄相关性黄斑变性的进展。 假设这些内表型受到常见和罕见变异组合的影响。 完成这些目标后，我们将在表型上定义年龄相关性黄斑变性的早期症状，以帮助我们了解这种疾病。 此外，我们将这些迹象与基因型联系起来，以定义遗传学在年龄相关性黄斑变性进展中的作用，以及结合基因型信息的新风险概况。

DESCRIPTION (provided by applicant): Through genetic analysis of case-control cohorts there has been remarkable progress in identifying genes for Age-Related Macular Degeneration. Most of these identifications have been accomplished through the interrogation of common variants. We will initiate the identification of rare variants in a founder population, the Amish, and use the whole exome chip to assess the association of Age-related Macular Degeneration with coding variants. We will further refine the Age-Related Macular Degeneration phenotype through the use of modern imaging, the OCT, to visualize the early anatomic signs of Age-Related Macular Degeneration. We hypothesize there are endophenotypes associated with specific genotypes that can be used to determine Age-related Macular Degeneration progression. These endophenotypes are hypothesized to be influenced by a combination of common and rare variants. Following the completion of these Aims, we will have phenotypically defined the early signs of Age-Related Macular Degeneration aiding our understanding of this disease. Moreover, we will relate these signs to genotypes to define the role of genetics in the progression of Age-Related Macular Degeneration and a new risk profile incorporating genotypic information.