Advancing Genetics Through the AMDgene Consortium

通过 AMDgene 联盟推进遗传学发展

• 批准号: 8655882
• 负责人: Jonathan L Haines
• 金额: $ 39.72万
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8655882
• 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; rare variant; 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.

摘要