Advancing Genetics Through the AMDgene Consortium

通过 AMDgene 联盟推进遗传学发展

• 批准号: 8265101
• 负责人: Jonathan L Haines
• 金额: $ 39.73万
• 依托单位: VANDERBILT 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 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265101
• 关键词: Address; Affect; Age; Age related macular degeneration; Architecture; Blindness; Clinical; Communication Methods; Consent; Data; Data Analyses; Data Set; Databases; Elderly; Electronic Mail; Environment; Ethics; Family; Funding; Genes; Genetic; Genetic Epistasis; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genome; Genotype; Goals; Haplotypes; Individual; Informed Consent; International; Measures; Meta-Analysis; Pathway interactions; Phenotype; Privacy; Reporting; Research Design; Research Infrastructure; Research Personnel; Resources; Risk; Role; Sample Size; Sampling; Site; TIMP3 gene; Teleconferences; Testing; Time; Update; Variant; case control; chemotactic factor inactivator; cost; data sharing; genetic analysis; genome wide association study; genome-wide; meetings; member; statistics; symposium; web site; working group

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the most common cause of severe vision loss among individuals over age 50 in the U.S. with millions of individuals around the world suffering severe vision loss. The influence of genetic variation on AMD is strong and through recent technological advances the genetic etiology of risk for AMD is being deconstructed. Independent studies have identified and confirmed variations in multiple genes that strongly affect risk to AMD, including CFH, HTRA1/ARMS2, C2/CFB, and C3 explaining a significant portion of the genetic risk for AMD. Initial efforts at genome-wide association studies have identified and/or confirmed several additional loci of more modest individual effect (CFI, LIPC, TIMP3), with many more loci providing suggestive associations. However, a substantial portion of the genetic architecture remains unexplained and detailed examination of effects specific to subtypes of AMD have been lacking. To address these deficiencies very large sample sizes of well characterized cases and controls and families are needed. Over the past year we have formed the AMDgene consortium to combine both samples and expertise. The initial goal of the consortium was a meta-analysis of existing GWAS data in a combined dataset of over 9,000 cases and 49,000 controls. Preliminary findings have identified new genome-wide significant loci. We have chosen an approach that maintains the primary data at each site, which promotes continued engagement by all participating sites, is cost and time efficient, and avoids potential consent, ethics, and privacy issues of sharing data collected under a wide variety of informed consent. The primary goal of this proposal is to support the AMDgene consortium effort through the following specific aims (1) Coordinate the activities of the AMDgene Consortium; (2) Add new datasets and augment current datasets; (3) Perform detailed meta-analyses on existing and new datasets; and (4) Perform detailed secondary analyses on these data. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) is the most common cause of severe vision loss among elderly individuals. Variations in multiple genes strongly affect risk to AMD but a substantial portion of the genetic architecture remains unexplained. The AMDgene international consortium was formed to aggregate existing genome-wide genotype data and to perform detailed meta-analyses to further understand the genetic underpinnings of AMD.

描述（由申请人提供）：年龄相关性黄斑变性 (AMD) 是美国 50 岁以上人群严重视力丧失的最常见原因，全世界有数百万人患有严重视力丧失。遗传变异对 AMD 的影响很大，并且通过最近的技术进步，AMD 风险的遗传病因学正在被解构。独立研究已经确定并证实了多个基因的变异对 AMD 风险有很大影响，包括 CFH、HTRA1/ARMS2、C2/CFB 和 C3，解释了 AMD 遗传风险的很大一部分。全基因组关联研究的初步工作已经确定和/或证实了几个具有更适度个体效应的其他位点（CFI、LIPC、TIMP3），还有更多位点提供了暗示性关联。然而，遗传结构的很大一部分仍然无法解释，并且缺乏对 AMD 亚型特有效应的详细检查。为了解决这些缺陷，需要非常大的、具有良好特征的病例、对照和家族的样本量。在过去的一年里，我们成立了 AMDgene 联盟，将样本和专业知识结合起来。该联盟的最初目标是对包含 9,000 多个病例和 49,000 个对照的组合数据集中的现有 GWAS 数据进行荟萃分析。初步研究结果已经确定了新的全基因组重要位点。我们选择了一种方法来维护每个站点的主要数据，从而促进所有参与站点的持续参与，具有成本效益和时间效率，并避免共享在各种知情同意下收集的数据的潜在同意、道德和隐私问题。该提案的主要目标是通过以下具体目标支持 AMDgene 联盟的努力： (1) 协调 AMDgene 联盟的活动； (2) 添加新的数据集并扩充现有数据集； (3) 对现有和新数据集进行详细的荟萃分析； (4) 对这些数据进行详细的二次分析。 公共卫生相关性：年龄相关性黄斑变性 (AMD) 是老年人严重视力丧失的最常见原因。多个基因的变异强烈影响 AMD 的风险，但遗传结构的很大一部分仍然无法解释。 AMDgene 国际联盟的成立是为了汇总现有的全基因组基因型数据并进行详细的荟萃分析，以进一步了解 AMD 的遗传基础。