International Advancing genomics through the AMD Genomics Consortium (IAMDGC)

通过 AMD 基因组联盟 (IAMDGC) 推进国际基因组学发展

• 批准号: 10471774
• 负责人: SUSAN HALLORAN BLANTON
• 金额: $ 45.54万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471774
• 关键词: Address; Admixture; Affect; Age related macular degeneration; Agreement; American; Antibodies; Biological; Biological Markers; Blindness; Caregivers; Clinical; Collaborations; Communication; Communities; Data; Data Set; Development; Diagnostic; Diet; Ethics; Etiology; Europe; Family; Family member; Foundations; Functional disorder; Funding; Fundus; Genes; Genetic; Genetic Variation; Genomics; Genotype; Goals; Grant; Health Care Costs; Heritability; Heterogeneity; Individual; Injections; Institution; International; Logistics; Measures; Meta-Analysis; Metadata; Mining; Participant; Pathway interactions; Pharmacologic Substance; Policies; Population; Prevention; Preventive measure; Procedures; Process; Quality of life; Research; Research Design; Resources; Risk; Sampling; Site; Smoking; Speed; Teleconferences; Testing; Trans-Omics for Precision Medicine; Treatment Protocols; Universities; Validation; Variant; Veterans; base; bevacizumab; biobank; case control; central database; clinical subtypes; cohort; computer infrastructure; cost; data access; data curation; data harmonization; data repository; database of Genotypes and Phenotypes; effective therapy; exome sequencing; genetic architecture; genetic pedigree; genome wide association study; genomic data; improved; large datasets; meetings; member; multi-ethnic; phenotypic biomarker; phenotypic data; programs; rare variant; repository; risk variant; social; treatment response; web site; working group

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.

与年龄有关的黄斑变性（AMD）是老年人视力丧失的主要原因，严重 影响受患者及其家人的独立性，生活质量和医疗费用。遗传 变化对AMD有重大影响，但目前只有大约一半的遗传力是。 了解AMD的遗传结构对于为AMD开发更好的治疗方法至关重要。这 国际AMD基因组学联盟（IAMDGC）组装了33个研究小组，过去四个 这笔赠款的多年通过扩大已知风险基因座的数量并牵涉到了重大进展 新的生物途径。这种更新将这些努力扩展到多个遗传祖先，研究设计和 更详细的表型数据。我们提出以下目标： 1）继续使用新数据集扩展IAMDGC资源。我们添加了七个新的 合作者，现在可以访问> 100,000名参与者的数据。 2）使用通用枢纽处理和共享基因组，表型和生物标志物数据。 Regeneron 药品已同意对大约40,000名参与者进行整个外显子组测序 赠款的成本。通过在其余的GWASE样品上统计归档，我们将创建一个极大的 数据集。我们将继续将数据包含在两个分析中心（美国和欧洲）中，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进行详细分析。数据集（87,542个案例/控件 和近6,000个家庭中的13,766个相关个体）可以测试许多遗传假设 潜在的临床亚型，生物标志物，稀有变体的影响以及跨遗传结构的变异性 祖先。合并基因组数据的初始处理和分析将通过此监督 申请和结果将适用于所有成员。我们有一个有效的过程，使成员能够 提出其他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的分析支持。 4）支持IAMDGC的物流和管理。成功的合作需要恒定 沟通和支持。我们将继续我们年度的IAMDGC特定面对面会议，下半场 - 参加ARVO年度会议的人以及定期电话会议的人会议。 我们的目标是极大地促进对AMD病理生理学的理解（使用基因组学作为我们的 基础指南），从而加快了AMD更好治疗和/或预防措施的发展。