Genetic Epidemiology of Age-Related Macular Degeneration in the Older Order Amish

老阿米什人年龄相关性黄斑变性的遗传流行病学

• 批准号: 8605190
• 负责人: Margaret A. Pericak-Vance
• 金额: $ 122.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605190
• 关键词: Address; Age related macular degeneration; Amish; Anatomy; Architecture; Biological; Biological Markers; Biology; Blindness; Caucasians; Caucasoid Race; Classification; Clinical; Code; Collection; Complex; Custom; DNA; Data; Data Set; Defect; Diet; Disease; Disease Progression; Enrollment; Environment; Eye; Family; Founder Generation; Frequencies; Genes; Genetic; Genomics; Genotype; Haplotypes; Hereditary Disease; Heritability; High Prevalence; Image; Indiana; Individual; Institutes; Knowledge; Life; Meta-Analysis; Molecular; Nuclear Family; Ohio; Pathway interactions; Patient Care; Pennsylvania; Phenotype; Population; Prevalence; Process; Relative (related person); Research; Resources; Risk; Risk Estimate; Role; Sampling; Smoking; Staging; Subgroup; Testing; Time; Universities; Variant; Visual impairment; base; case control; cohort; complement system; design; endophenotype; exome; exome sequencing; genetic analysis; genetic association; genetic epidemiology; genetic pedigree; genetic variant; genome sequencing; improved; insight; novel; public health relevance; rare variant; tomography; trait

DESCRIPTION (provided by applicant): Through genetic analysis of case-control cohorts there has been remarkable progress in identifying genes for Age-Related Macular Degeneration. Most of these identifications have been accomplished through the interrogation of common variants. We will initiate the identification of rare variants in a founder population, the Amish, and use the whole exome chip to assess the association of Age-related Macular Degeneration with coding variants. We will further refine the Age-Related Macular Degeneration phenotype through the use of modern imaging, the OCT, to visualize the early anatomic signs of Age-Related Macular Degeneration. We hypothesize there are endophenotypes associated with specific genotypes that can be used to determine Age-related Macular Degeneration progression. These endophenotypes are hypothesized to be influenced by a combination of common and rare variants. Following the completion of these Aims, we will have phenotypically defined the early signs of Age-Related Macular Degeneration aiding our understanding of this disease. Moreover, we will relate these signs to genotypes to define the role of genetics in the progression of Age-Related Macular Degeneration and a new risk profile incorporating genotypic information.

描述（由申请人提供）：通过病例对照队列的遗传分析，在鉴定与视网膜相关的黄斑变性的基因方面取得了显著进展。 大多数这些鉴定是通过询问常见的变体来完成的。 我们将开始在创始人人群中识别罕见的变异，Amish，并使用整个外显子组芯片来评估与编码变异相关的黄斑变性的关联。 我们将通过使用现代成像（OCT）进一步细化视网膜相关黄斑变性表型，以可视化视网膜相关黄斑变性的早期解剖学体征。 我们假设存在与特定基因型相关的内表型，可用于确定视网膜相关黄斑变性进展。 假设这些内表型受常见和罕见变体的组合的影响。 在完成这些目标之后，我们将在表型上确定视网膜相关黄斑变性的早期体征，以帮助我们了解这种疾病。 此外，我们将把这些迹象与基因型联系起来，以确定遗传学在黄斑变性进展中的作用，并结合基因型信息建立一个新的风险特征。