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: 10703460
• 负责人: SUSAN HALLORAN BLANTON
• 金额: $ 52.54万
• 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/10703460
• 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; Maps; Measures; Meta-Analysis; Metadata; Mining; Participant; Pathway interactions; Pharmacologic Substance; Phenotype; 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; 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 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.

年龄相关性黄斑变性（AMD）是美国老年人视力丧失的主要原因，并且严重 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有重大影响，但目前仅了解大约一半的遗传力。 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 国际 AMD 基因组学联盟 (IAMDGC) 已组建了 33 个研究小组，在过去的四年里 多年的这笔赠款通过扩大已知风险位点的数量并暗示了这一点，取得了重大进展 新的生物学途径。这一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）继续用新的数据集扩展IAMDGC资源。我们添加了七个新的 协作者，现在可以访问超过 100,000 名参与者的数据。 2) 使用通用中心处理和共享基因组、表型和生物标记数据。再生元 Pharmaceuticals 已同意对约 40,000 名参与者进行全外显子组测序，无需任何费用 补助金的费用。通过对剩余的 GWAS 样本进行统计插补，我们将创建一个非常大的样本 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进行详细分析。数据集（87,542 例/对照 以及近 6,000 个家庭的 13,766 名相关个体）能够测试众多遗传假设 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步处理和分析将通过此监督 申请和结果将向所有成员公开。我们有一个高效的流程，允许会员 提出更多的研究和更广泛的研究团体来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。成功的合作需要不断的 沟通和支持。我们将继续每年一度的 IAMDGC 面对面会议，下半年- 为参加 ARVO 年会的人员举办日间会议，以及定期电话会议。 我们的目标是极大地增进对 AMD 病理生理学的理解（使用基因组学作为我们的研究对象） 基础指南），从而加速 AMD 更好的治疗和/或预防的开发。

项目成果

Pharmacogenetic associations with long-term response to anti-vascular endothelial growth factor treatment in neovascular AMD patients

新生血管性 AMD 患者抗血管内皮生长因子治疗的长期反应与药物遗传学相关

• 发表时间: 2014-12-19
• 期刊: Molecular Vision
• 影响因子: 2.2
• 作者: U. Park;J. Shin;L. McCarthy;S. Kim;J. Park;Hum Chung;H. Yu
• 通讯作者: H. Yu

Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs.

来自多中心德国队列的 335 名斯塔加特病患者的 ABCA4 基因突变谱 - 选定的深内含子变异和常见 SNP 的影响。

• 发表时间: 2017-01-01
• 影响因子: 4.4
• 作者: Schulz, Heidi L;Grassmann, Feli;Kellner, Ulrich;Spital, Georg;Rüther, Klaus;Jägle, Herbert;Hufendiek, Karsten;Rating, Philipp;Huchzermeyer, Cord;Baier, Maria J;Weber, Bernhard H F;Stöhr, Heidi
• 通讯作者: Stöhr, Heidi

Common haplotypes at the CFH locus and low-frequency variants in CFHR2 and CFHR5 associate with systemic FHR concentrations and age-related macular degeneration.

CFH 基因座的常见单倍型以及 CFHR2 和 CFHR5 的低频变异与全身 FHR 浓度和年龄相关性黄斑变性相关。

• 发表时间: 2021-08-05
• 影响因子: 9.8
• 作者: Lorés;van Beek, Anna E;Willems, Esther;Zandstra, Judith;van Mierlo, Gerard;Einhaus, Alfred;Mary, Jean;Stucki, Corinne;Bakker, Bjorn;Hoyng, Carel B;Fauser, Sascha;Clark, Simon J;de Jonge, Marien I;Nogoceke, Everson;Koertvely
• 通讯作者: Koertvely

Geographic distribution of rare variants associated with age-related macular degeneration

与年龄相关性黄斑变性相关的罕见变异的地理分布

• DOI: 10.1007/s12206-013-0313-6
• 发表时间: 2018-01-27
• 期刊: Molecular Vision
• 影响因子: 2.2
• 作者: M. Geerlings;E. Kersten;J. Groenewoud;L. Fritsche;C. Hoyng;E. D. de Jong;A. D. den Holl;er;er
• 通讯作者: er

The Application of Genetic Risk Scores in Age-Related Macular Degeneration: A Review.

遗传风险评分在年龄相关性黄斑变性中的应用：综述。

• 发表时间: 2016-03-04
• 作者: Cooke Bailey, Jessica N;Hoffman, Joshua D;Sardell, Rebecca J;Scott, William K;Pericak;Haines, Jonathan L
• 通讯作者: Haines, Jonathan L