Integrative Data Analysis for Refractive Error

屈光不正的综合数据分析

基本信息

批准号：
8842641
负责人：
Dwight Edward Stambolian
金额：
$ 39.2万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8842641
关键词：
12 year old Accounting Address Affect Angle-Closure Glaucoma Animal Model Architecture Asians Bioinformatics Biological Biomedical Research Blindness Caucasians Choroidal Neovascularization Collaborations Complex Complication Data Data Analyses Data Set Diabetic Retinopathy Disease Education Environment Environmental Risk Factor Eye Eye diseases Family Gene Frequency Genes Genetic Genetic Predisposition to Disease Genetic Risk Genetic Variation Genome Genotype Glaucoma Goals Health Health system Heritability Human Identifications Hyperopia Individual International Lead Left Location Measurement Measures Meta-Analysis Minor Modeling Morphology Myopia Ocular Hypertension Open-Angle Glaucoma Optic Disk Optics Pathway interactions Patients Persons Pharmaceutical Preparations Physiologic Intraocular Pressure Play Population Prevalence Public Health Refractive Errors Regulatory Pathway Reporting Retinal Detachment Risk Risk Factors Role Sample Size Sampling Secondary to Susceptibility Gene Testing Topical application United States Variant Vascularization Visual Acuity Visual impairment Visually Impaired Persons Work case control cohort cost economic impact endophenotype exome gene environment interaction gene interaction genetic technology genetic variant genome wide association study genome-wide health economics meetings new therapeutic target novel novel therapeutics pressure prevent rare variant research study risk variant success trait

项目摘要

DESCRIPTION (provided by applicant): Refractive error is the most common eye disorder in the world, and its public health and economic impact are considerable. Treatment of the U.S population for refractive error costs twice as much as glaucoma and 10x the amount for AMD or diabetic retinopathy and is a major burden to the U.S. public health system. Current treatments for refractive error are not directed at the secondary complications. Such complications include choroidal neovascularization, retinal detachment and glaucoma. Glaucoma is a complication of myopia~ prevalence of glaucoma is 4.2% in eyes with low myopia and 4.4% of eyes with moderate to high myopia compared to 1.5% of eyes without myopia. Individuals with hyperopia are 40% more likely to develop ocular hypertension than those who are emmetropic. Retinal detachment is increased in eyes with refractive error~ risk of retinal detachment is increased 4-10 fold in myopic eyes. Finally, the risk for choroidal neo-vascularization is increased from 2-fold for mild myopia to 9-fold for severe myopia. Current treatments do not prevent the ocular complications secondary to refractive error because they are not targeted at stopping progression of refractive error. Previous attempts to control progression of refractive error with optical and drug approaches have met with limited success. There is extensive evidence for significant heritable components for hyperopia and myopia. If one can identify the genes involved in these disorders, one can identify unsuspected disease mechanisms, develop animal models of these mechanisms and use these models to develop and test new treatments, identify interactions of these genes with modifiable environmental risk factors, and treat people very early in the course of the disease to prevent secondary complications. One of the major challenges now facing biomedical research is the discovery of specific disease mechanisms that underlie heritable disorders that display a complex mode of inheritance. This includes complex eye diseases such as refractive error. An appealing hypothesis is that sequence variations play an important role in refractive error similar to other complex diseases. Advances in genetic technology and bioinformatics have made it possible to perform experiments that examine hundreds of thousands of genetic variants in large numbers of individuals and to determine their location and significance for influencing disease. In this proposal, we will extend our previous CREAM work to identify the underlying genetic variation influencing refractive error. This work will take advantage of already acquired GWAS and exome chip data from multiple cohorts to identify the underlying genetic variants modifying refractive error. We will also extend our analysis to identify gene-environment interactions in our cohorts as well as determine any potential overlap between the glaucoma and RE genes.

描述（由申请人提供）：屈光不正是世界上最常见的眼部疾病，其对公共健康和经济的影响相当大。美国人口屈光不正的治疗费用是青光眼的两倍，是 AMD 或糖尿病视网膜病变的 10 倍，是美国公共卫生系统的主要负担。目前屈光不正的治疗方法并不针对继发性并发症。这些并发症包括脉络膜新生血管、视网膜脱离和青光眼。青光眼是近视的并发症，低度近视眼中青光眼的患病率为4.2%，中高度近视眼中青光眼的患病率为4.4%，而非近视眼中青光眼的患病率为1.5%。远视眼患者患高眼压症的可能性比正视眼患者高 40%。屈光不正的眼睛视网膜脱离的风险增加~近视眼视网膜脱离的风险增加4-10倍。最后，脉络膜新生血管形成的风险从轻度近视的2倍增加到重度近视的9倍。目前的治疗方法不能预防屈光不正继发的眼部并发症，因为它们的目标不是阻止屈光不正的进展。先前尝试通过以下方法控制屈光不正的进展：光学和药物方法取得的成功有限。有大量证据表明远视和近视具有显着的遗传因素。如果人们能够识别出与这些疾病有关的基因，就可以识别出未被怀疑的疾病机制，开发这些机制的动物模型，并使用这些模型来开发和测试新的治疗方法，识别这些基因与可改变的环境风险因素的相互作用，并以非常好的方式治疗人们。在病程早期预防继发并发症。生物医学研究目前面临的主要挑战之一是发现表现出复杂遗传模式的遗传性疾病背后的特定疾病机制。这包括复杂的眼部疾病，例如屈光不正。一个有吸引力的假设是，与其他复杂疾病类似，序列变异在屈光不正中发挥着重要作用。遗传技术和生物信息学的进步使得能够进行实验来检查大量个体中的数十万个遗传变异，并确定它们的位置和影响疾病的重要性。在本提案中，我们将扩展之前的 CREAM 工作，以确定影响屈光不正的潜在遗传变异。这项工作将利用已经获得的来自多个队列的 GWAS 和外显子组芯片数据来识别改变屈光不正的潜在遗传变异。我们还将扩展我们的分析，以确定我们的队列中基因与环境的相互作用，并确定青光眼和 RE 基因之间任何潜在的重叠。