International Advancing genomics through the AMD Genomics Consortium (IAMDGC)

老年性黄斑变性(AMD)是美国老年人视力丧失的主要原因之一，严重 影响患者及其家人的独立性、生活质量和医疗费用。遗传 变异对AMD有很大的影响，但目前只有大约一半的遗传性被理解。 了解AMD的遗传结构对于开发更好的AMD治疗方法至关重要。这个 国际AMD基因组联合会(IAMDGC)组建了33个研究小组，在过去的四年中 多年来，这笔赠款通过扩大已知风险基因座的数量并牵涉到 新的生物途径。这种更新将这些努力扩展到多个基因祖先、研究设计和 更详细的表型数据。我们提出以下目标： 1)继续用新的数据集扩大IAMDGC资源。我们增加了七个新的 协作者，现在可以访问&>100,000名参与者的数据。 2)使用通用中心处理和共享基因组、表型和生物标志物数据。再生 制药公司已同意对大约40,000名参与者进行完整的外显子组测序 助学金的成本。通过对剩余的GWASD样本进行统计归因于，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)对广泛的结果数据集执行详细分析。数据集(87,542个病例/对照 以及近6,000个家庭的13,766个相关个体)使许多遗传假说得以检验 潜在的临床亚型、生物标记物、罕见变异的影响以及以下遗传结构的可变性 祖先。联合基因组数据的初始处理和分析将通过此进行监督 申请和结果将向所有成员开放。我们有一个高效的流程，允许成员 提出更多研究和更广泛的研究社区，以访问这些数据和计算和 通过适当的分析中心提供分析支持。 4)支持IAMDGC的后勤和行政管理。成功的协作需要持续不断 沟通和支持。我们将继续我们每年一度的IAMDGC面对面会议，下半年- 出席ARVO年度会议的人员的日会议，以及定期的电话会议。 我们的目标是大大提高对AMD病理生理学的理解(使用基因组学作为我们的 基础指南)，从而加快AMD更好的治疗和/或预防的开发。

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.