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）：与年龄相关的黄斑变性（AMD）是美国50岁以上个人严重视力丧失的最常见原因，世界各地数百万个人遭受严重的视力丧失。遗传变异对AMD的影响很强，通过最近的技术进步，AMD风险的遗传病因正在解构。独立研究已经确定并确认了多种基因的变化，这些基因强烈影响AMD的风险，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努力已经确定和/或确认了一些更适度的个人效应（CFI，LIPC，TIMP3）的其他基因座，其中更多的基因座提供了暗示性的关联。然而，遗传结构的很大一部分仍无法解释，并且缺乏对AMD亚型特定影响的详细研究。为了解决这些缺陷，需要很大的样本大小，包括良好的案例，对照和家庭。在过去的一年中，我们组建了Amdgene财团，以结合样品和专业知识。该联盟的最初目标是在9,000多个病例和49,000个控制的组合数据集中对现有GWAS数据进行的荟萃分析。初步发现已经确定了全基因组明显的基因座。我们选择了一种维护每个站点的主要数据的方法，该方法促进了所有参与站点的持续参与，是成本和时间的效率，并避免了在各种知情同意下共享数据的潜在同意，道德和隐私问题。该提案的主要目的是通过以下特定目标（1）协调Amdgene联盟的活动； （2）添加新数据集和增强当前数据集； （3）对现有数据集和新数据集执行详细的荟萃分析； （4）对这些数据进行详细的辅助分析。 公共卫生相关性：与年龄相关的黄斑变性（AMD）是老年人严重视力丧失的最常见原因。多个基因的变化强烈影响对AMD的风险，但是遗传结构的很大一部分仍无法解释。 AMDGENE国际联盟旨在汇总现有的全基因组基因型数据并执行详细的荟萃分析，以进一步了解AMD的遗传基础。