Etiologic Studies of Age-Related Macular Degeneration

描述（由申请人提供）：我们将建立在已建立和最近确定的遗传基因座和环境和眼部决定因素的基础上，将本提案中确定的年龄相关性黄斑变性（AMD）新发现的基因座纳入基因-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罕见的、潜在的功能性变体的全谱，以及候选基因/区域中的常见变体。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。对因果变异的了解将导致AMD更准确的定义和分类系统。我们将扩大我们独特的数据库，以实现研究的科学目标，并促进与其他研究人员的合作。我们还将进行功能研究，以确定与遗传变异相关的机制。作为这项工作的结果，我们预计，将确定额外的新的致病性遗传途径，这种日益增加的失明原因。这些潜在的发现将导致新的治疗和预防措施，以保护视力，并将减少由于AMD的先进形式的显着视力丧失的负担。

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.