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 VA百万退伍军人计划（MVP）提供了对基因分型和纵向临床数据的访问权限 超过616,000名退伍军人，从而提供无与伦比的机会来定义 复杂的疾病。在这个项目中，我们将检查与年龄相关的眼睛状况高度相关的眼睛状况 对退伍军人卫生管理局（主要的开角型青光眼，糖尿病性视网膜病，富氏 内皮角膜营养不良，白内障，近视，泪水缺乏症）在 退伍军人人口对视力和对系统资源的需求有明显的不利影响。在AIM 1中， 我们将为每个眼表型执行单个变体分析，以识别共同和 稀有变体。在开发鲁棒算法到to之后，将进行这种遗传分析 识别有条件和控制的情况，没有这种情况。该算法将基于 国际疾病分类（ICD）代码。单独的基因组宽结合研究（GWAS） 将对欧美（EA），非裔美国人（AA）或西班牙裔美国人的MVP参与者进行 美国（HA）下降，通过主要成分分析证实下降。其中许多 条件，这将是有史以来第一个进行的GWA，或者是第一个跨种族GWA。这项工作 将跟随我们对年龄相关的黄斑变性（AMD）的成功分析，我们指出 与AA和HA退伍军人相比，EA遗传基础的显着差异。在AIM 2中，我们将使用 PHEWAS分析以了解不同的眼疾病之间的相互关系 眼部疾病和其他疾病以及眼部疾病和定量生理特征之间。 MVP生物库提供了一个前所未有的机会来检查眼病的遗传基础 这会影响退伍军人的人口，并确定眼部疾病和其他医疗状况如何 通过共享基因变异或遗传谱相关。通过确定新关系 在眼部特征和其他疾病或生理措施之间，该项目将解决重要的 眼部遗传学领域的间隙。