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

摘要 VA百万退伍军人计划（MVP）提供了基因分型和纵向临床数据， 超过616，000名退伍军人，从而提供了一个无与伦比的机会，以确定遗传基础， 复杂的疾病。在这个项目中，我们将研究与年龄相关的眼部疾病， 退伍军人健康管理局（原发性开角型青光眼，糖尿病视网膜病变，Fuchs 角膜内皮营养不良、白内障、近视、水性泪液缺乏），这些疾病在 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， 我们将对每种眼部表型进行单变异分析，以鉴定常见的， 罕见的变种该遗传分析将在开发出一种稳健的算法后进行， 标识具有条件的病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） 将在欧洲裔美国人（EA）、非洲裔美国人（AA）或西班牙裔美国人的MVP入组者中进行- 美国人（HA）血统，通过主成分分析确认血统。对于许多这些 在这种情况下，这将是有史以来第一次进行GWAS，或者将是第一次跨种族的GWAS。这项工作 将继续我们对年龄相关性黄斑变性（AMD）的成功分析， 显着差异的遗传基础EA相比，AA和HA退伍军人。在目标2中，我们将使用 PheWAS分析，以了解不同眼科疾病之间的相互关系， 眼科疾病和其他病症之间的关系以及眼科疾病和数量生理性状之间的关系。 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 影响退伍军人群体，并确定如何眼科疾病和其他医疗条件是 通过共享的基因变体或遗传图谱相关。通过识别新的关系 在眼部特征和其他疾病或生理措施之间，该项目将解决一个重要的 眼遗传学领域的空白。

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.