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

描述（由申请人提供）：通过病例对照队列的遗传分析，在鉴定与视网膜相关的黄斑变性的基因方面取得了显著进展。 大多数这些鉴定是通过询问常见的变体来完成的。 我们将开始在创始人人群中识别罕见的变异，Amish，并使用整个外显子组芯片来评估与编码变异相关的黄斑变性的关联。 我们将通过使用现代成像（OCT）进一步细化视网膜相关黄斑变性表型，以可视化视网膜相关黄斑变性的早期解剖学体征。 我们假设存在与特定基因型相关的内表型，可用于确定视网膜相关黄斑变性进展。 假设这些内表型受常见和罕见变体的组合的影响。 在完成这些目标之后，我们将在表型上确定视网膜相关黄斑变性的早期体征，以帮助我们了解这种疾病。 此外，我们将把这些迹象与基因型联系起来，以确定遗传学在黄斑变性进展中的作用，并结合基因型信息建立一个新的风险特征。

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.