Advancing Genetics Through the AMDgene Consortium

通过 AMDgene 联盟推进遗传学发展

• 批准号: 8449079
• 负责人: Jonathan L Haines
• 金额: $ 36.54万
• 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 2013-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449079
• 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

ABSTRACT 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.

抽象的 与年龄相关的黄斑变性（AMD）是个体严重视力丧失的最常见原因 在美国，超过50岁以上，世界各地数百万人遭受严重的视力丧失。影响 AMD的遗传变异很强，通过最近的技术进步，遗传病因的风险 AMD正在解构。独立研究已经确定并确认了多个基因的变化 强烈影响对AMD的风险，包括CFH，HTRA1/ARMS2，C2/CFB和C3的风险 AMD遗传风险的一部分。全基因组协会研究的初步努力已经确定和/或 确认了更多适度的个人效果（CFI，LIPC，Timp3）的其他基因座，还有更多基因座 提供暗示性的关联。但是，遗传结构的很大一部分仍然存在 缺乏对AMD亚型特定效果的无法解释和详细的检查。解决 这些缺陷需要很大的样本量，包括表征良好的病例和对照和家庭。 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。这 财团的最初目标是对9,000多个合并数据集中现有GWAS数据的荟萃分析 病例和49,000个对照。初步发现已经确定了全基因组明显的基因座。我们有 选择了一种在每个站点上维护主要数据的方法，该方法促进了所有人的继续参与 参与站点是成本和时间效率的，避免了共享的潜在同意，道德和隐私问题 根据多种知情同意的数据收集的数据。该提议的主要目标是支持 通过以下特定目的（1）协调Amdgene的活动 财团； （2）添加新数据集和增强当前数据集； （3）对 现有和新数据集：; （4）对这些数据进行详细的辅助分析。