International Advancing genomics through the AMD Genomics Consortium (IAMDGC)

视网膜相关性黄斑变性（AMD）是美国老年人视力丧失的主要原因， 影响患者及其家庭的独立性、生活质量和医疗费用。遗传 变异对AMD有重大影响，但目前仅了解约一半的遗传性。 了解AMD的遗传结构对于开发更好的AMD治疗方法至关重要。的 国际AMD基因组学联盟（IAMDGC）已经组建了33个研究小组， 多年来，这项赠款通过扩大已知风险位点的数量和 新的生物学途径。这种更新将这些努力扩展到多个遗传祖先，研究设计， 更详细的表型数据。我们提出以下目标： 1)继续使用新的数据集扩展IAMDGC资源。我们新增了7个 合作者，现在可以访问来自> 100，000名参与者的数据。 2)使用通用集线器处理和共享基因组、表型和生物标志物数据。Regeneron 制药公司已同意对大约40，000名参与者进行全外显子组测序， 费用补助金。通过对剩余GWAS样本的统计插补，我们将创建一个非常大的 数据集。我们将继续将数据存放在两个分析中心（美国和欧洲），以简化访问并提供 计算和分析支持。 3)对生成的大量数据集执行详细分析。数据集（87，542例病例/对照） 和近6,000个家庭中的13,766个相关个体）使得许多遗传假设得以检验 潜在的临床亚型，生物标志物，罕见变异的影响，以及遗传结构的变异性。 祖先组合基因组数据的初始处理和分析将通过此 所有会员均可查阅申请表及结果。我们有一个有效的程序，允许成员 提出更多的研究和更广泛的研究社区，以访问这些数据和计算， 通过适当的分析中心提供分析支持。 4)支持机构间灾害管理和灾害控制理事会的后勤和行政工作。成功的合作需要不断 沟通和支持。我们将继续每年举行一次专门针对机构间移徙和发展理事会的面对面会议，下半年- 为参加ARVO年会的人举行一天的会议，并定期举行电话会议。 我们的目标是大大推进AMD病理生理学的理解（使用基因组学作为我们的 基础指南），从而加速开发更好的AMD治疗和/或预防。

Age-related macular degeneration (AMD) is a leading cause of vision loss in older Americans and severely impacts the independence, quality of life, and healthcare costs for those afflicted and their families. Genetic variation has a major influence on AMD, but only about half of the heritability is currently understood. Understanding the genetic architecture of AMD is critical for developing better treatments for AMD. The International AMD Genomics Consortium (IAMDGC) has assembled 33 research groups and over the past four years of this grant has enabled significant progress by extending the number of known risk loci and implicating new biological pathways. This renewal extends these efforts to multiple genetic ancestries, study designs, and more detailed phenotypic data. We propose the following aims: 1) Continue to expand the IAMDGC resource with new datasets. We have added seven new collaborators and now have access to data from >100,000 participants. 2) Use universal hubs to process and share genomic, phenotypic, and biomarker data. Regeneron Pharmaceuticals has agreed to conduct whole exome sequencing on approximately 40,000 participants at no cost to the grant. By statistical imputation on the remaining GWASed samples, we will create an extremely large dataset. We will continue to house the data in two analytic hubs (US and Europe) to simplify access and provide computational and analytic support. 3) Perform detailed analyses on the extensive resulting dataset. The dataset (87,542 cases/controls and 13,766 related individuals in nearly 6,000 families) enables testing of numerous genetic hypotheses underlying clinical subtypes, biomarkers, effects of rare variants, and variability in the genetic architecture across ancestries. The initial processing and analysis of the combined genomic data will be overseen through this application and results will be available to all members. We have an efficient process allowing members to propose additional studies and the broader research community to access these data and computational and analytical support through the appropriate analytic hub. 4) Support the logistics and administration of the IAMDGC. Successful collaboration requires constant communication and support. We will continue our yearly IAMDGC-specific face-to-face meeting, a second half- day meeting for those attending the ARVO annual meeting, and regular teleconference calls. Our goal is to greatly advance the understanding of AMD pathophysiology (using genomics as our foundational guide) and thus speed the development of better treatments and/or preventions of AMD.