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: 8460277
• 负责人: Margaret A. Pericak-Vance
• 金额: $ 124.19万
• 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/8460277
• 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; 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）：通过对病例对照组的遗传分析，在鉴定与年龄相关的黄斑变性基因的基因方面取得了显着进展。 这些标识大多数是通过审问共同变体来完成的。 我们将启动对基础人群（Amish）中稀有变体的鉴定，并使用整个外显子芯片评估与年龄相关的黄斑变性与编码变体的关联。 我们将通过使用现代成像（OCT）来形象化与年龄相关的黄斑变性的早期解剖迹象，进一步完善与年龄相关的黄斑变性表型。 我们假设存在与特定基因型相关的内型型，可用于确定与年龄相关的黄斑变性进展。 这些内型型被假设是受共同变体和稀有变体的组合的影响。 这些目标完成后，我们将在表型上定义与年龄相关的黄斑变性的早期迹象，以帮助我们对这种疾病的理解。 此外，我们将将这些迹象与基因型联系起来，以定义遗传学在与年龄相关的黄斑变性的进展中的作用，并结合了基因型信息的新风险概况。