Etiologic Studies of Age-Related Macular Degeneration

描述（由申请人提供）：我们将建立在已建立的和最近确定的遗传位点以及环境和眼部决定因素的基础上，结合本提案中确定的年龄相关性黄斑变性（AMD）新发现的位点，进行基因-基因，基因-环境和预测建模分析。我们还建议通过靶向测序来评估候选基因/区域中罕见的、潜在的功能变异以及常见变异的全谱。相关基因中因果变异的发现将提高对AMD发展和进展的潜在机制的理解。因果变异的知识将导致AMD更准确的定义和分类系统。我们将扩展我们独特的数据库，以完成研究的科学目标，并促进与其他研究者扩大合作。我们还将进行功能研究，以确定与遗传变异相关的机制。由于这一努力，我们预计将为这一日益增加的致盲原因确定更多新的致病遗传途径。这些潜在的发现将为保护视力带来新的治疗和预防措施，并将减轻由于晚期AMD导致的明显视力丧失的负担。

DESCRIPTION (provided by applicant): We will build upon the established and recently identified genetic loci and environmental and ocular determinants, to incorporate newly discovered loci for age-related macular degeneration (AMD) identified in this proposal for gene-gene, gene-environment, and predictive modeling analyses. We also propose to assess the full spectrum of rare, potentially functional variants, as well as common variants in candidate genes/regions by targeted sequencing. The discovery of causal variants in associated genes will improve the understanding of the underlying mechanisms of AMD development and progression. Knowledge of causal variants will lead to more accurate definitions and classification systems for AMD. We will expand our unique databases to accomplish the scientific aims of the study and to facilitate expanded collaborative efforts with other investigators. We will also conduct functional studies to define the mechanisms associated with the genetic variants. As a result of this effort, we anticipate that additional new pathogenic genetic pathways will be identified for this increasing cause of blindness. These potential discoveries will lead to novel therapeutic and preventive measures for preserving vision, and will reduce the burden of marked visual loss due to the advanced forms of AMD. PUBLIC HEALTH RELEVANCE: We will expand knowledge about the genetic architecture of age-related macular degeneration (AMD) by identifying new genetic loci as well as how behaviors and modifiable factors increase or decrease genetic susceptibility. Discovery of new genetic markers which are pathogenic and have a strong influence on AMD will lead to new treatments. Experimental studies will identify the mechanisms related to the newly discovered genetic variants.