Deciphering Genetic and Environmental Influences on Visual Disorders in the Million Veteran Program

解读百万退伍军人计划中遗传和环境对视觉障碍的影响

• 批准号: 10158432
• 负责人: NEAL S. PEACHEY
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158432
• 关键词: Address; Adverse effects; African; African American; Age; Age related macular degeneration; Algorithms; American; Biological Markers; Blindness; Cataract; Clinical; Clinical Data; Complex; Data; Databases; Development; Diabetic Retinopathy; Diagnosis; Disease; Electronic Health Record; Environmental Exposure; Environmental Risk Factor; Ethnic group; European; Eye; Eye diseases; Fuchs' Endothelial Dystrophy; Funding; Genes; Genetic; Genetic Identity; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genotype; Glaucoma; Glucose; Haplotypes; Health; Heritability; Heterogeneity; Hispanic Americans; Hispanics; Informatics; Infrastructure; International Classification of Disease Codes; Investigation; Lipids; Measures; Medical; Modeling; Myopia; Ocular Hypertension; Outcome; Pathway interactions; Phase; Phenotype; Physiological; Population Programs; Primary Open Angle Glaucoma; Principal Component Analysis; Privatization; Process; Quality Control; Refractive Errors; Resources; Review Literature; Risk; Role; SNP array; Sampling; Smoking; Smoking Status; Suggestion; Surveys; Susceptibility Gene; System; Testing; United States Department of Veterans Affairs; Variant; Veterans; Veterans Health Administration; Vision; Vision Disorders; Visual impairment; Work; admixture mapping; age related; aqueous; base; biobank; case control; disease phenotype; eye dryness; genetic analysis; genetic architecture; genetic risk factor; genetic variant; genome wide association study; genome-wide; genomic locus; military veteran; multi-ethnic; multiple chronic conditions; novel; phenome; polygenic risk score; programs; racial and ethnic; rare variant; risk sharing; sex; trait; visual dysfunction

Abstract The VA Million Veteran Program (MVP) provides access to genotyping and longitudinal clinical data for more than 616,000 Veterans, thereby offering an unparalleled opportunity to define the genetic basis of complex diseases. In this project, we will examine age-related eye conditions that are of high relevance to the Veterans Health Administration (primary open angle glaucoma, diabetic retinopathy, Fuchs endothelial corneal dystrophy, cataract, myopia, aqueous tear deficiency) that are prevalent in the Veteran population with distinct adverse effects on vision and demands on system resources. In Aim 1, we will perform single variant analysis for each ocular phenotype, towards identification of common and rare variants. This genetic analysis will be conducted following development of a robust algorithm to identify Cases with a condition and Controls without that condition. This algorithm will be based on International Classification of Diseases (ICD) codes. Separate genome wide association studies (GWAS) will be conducted on MVP enrollees of European-American (EA), African-American (AA) or Hispanic- American (HA) descent, with descent confirmed by Principal Component Analysis. For many of these conditions, this will be the first GWAS ever conducted or will be the first trans-ethnic GWAS. This work will follow-on our successful analysis of age-related macular degeneration (AMD), where we noted marked differences in the genetic basis of EA as compared to AA and HA Veterans. In Aim 2, we will use PheWAS analysis to understand the interrelationships between different ocular diseases, between ocular diseases and other conditions and between ocular diseases and quantitative physiological traits. The MVP biobank provides an unprecedented opportunity to examine the genetic basis for eye diseases that impact Veteran populations and to determine how eye diseases and other medical conditions are related via shared gene variants or genetic profiles. Through the identification of new relationships between ocular traits and other diseases or physiologic measures, this project will address an important gap in the ocular genetics field.

抽象的 退伍军人管理局百万退伍军人计划 (MVP) 提供基因分型和纵向临床数据的访问 超过 616,000 名退伍军人，从而提供了一个无与伦比的机会来定义遗传基础 复杂的疾病。在这个项目中，我们将检查与年龄相关的高度相关的眼部状况 退伍军人健康管理局（原发性开角型青光眼、糖尿病性视网膜病变、福克斯 内皮性角膜营养不良、白内障、近视、水性泪液缺乏症） 对视力和系统资源需求有明显不利影响的退伍军人群体。在目标 1 中， 我们将对每种眼表型进行单变异分析，以识别常见和 罕见的变种。该遗传分析将在开发出强大的算法后进行 识别具有条件的案例和不具有该条件的对照。该算法将基于 国际疾病分类 (ICD) 代码。单独的全基因组关联研究 (GWAS) 将对欧洲裔美国人 (EA)、非洲裔美国人 (AA) 或西班牙裔美国人的 MVP 登记者进行 美国 (HA) 血统，通过主成分分析确认血统。对于其中许多 如果条件允许的话，这将是有史以来第一次进行的 GWAS，或者将是第一次跨种族的 GWAS。这部作品 将继续我们对年龄相关性黄斑变性 (AMD) 的成功分析，我们注意到 与 AA 和 HA 退伍军人相比，EA 的遗传基础存在显着差异。在目标 2 中，我们将使用 PheWAS 分析可了解不同眼部疾病之间的相互关系 眼部疾病与其他状况以及眼部疾病与定量生理特征之间的关系。 MVP 生物库为检查眼部疾病的遗传基础提供了前所未有的机会 影响退伍军人群体并确定眼部疾病和其他医疗状况的情况 通过共享基因变体或遗传图谱相关。通过识别新的关系 在眼部特征与其他疾病或生理测量之间，该项目将解决一个重要问题 眼遗传学领域的空白。