Genetic Epidemiology of Refractive Error

屈光不正的遗传流行病学

基本信息

批准号：
8512728
负责人：
Dwight Edward Stambolian
金额：
$ 36.48万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8512728
关键词：
Achievement Alleles Anatomy Animal Model Bioinformatics Biological Biology Biomedical Research Canada Categories Caucasians Caucasoid Race Choroidal Neovascularization Chromosomes, Human, Pair 22 Complex Complication DNA Data Diabetic Retinopathy Disease Elements Environment Environmental Risk Factor Epidemiologic Studies Europe Eye Eye diseases Family Frequencies Gender Genes Genetic Genetic Determinism Genome Genotype Glaucoma Health system Human Human Identifications Hyperopia Individual Inherited Lead Location Macular degeneration Maps Meta-Analysis Microsatellite Repeats Modeling Myopia Ocular Hypertension Optics Pathway interactions Patients Pharmaceutical Preparations Play Population Prevalence Process Public Health Refractive Errors Regulatory Pathway Research Research Personnel Resources Retinal Detachment Risk Role Sampling Scanning Secondary to Signal Transduction Single Nucleotide Polymorphism Staging Testing Variant Vision Work abstracting age effect cohort cost economic impact follow-up gene interaction genetic epidemiology genetic technology genetic variant genome wide association study genome-wide health economics high risk insight instrument meetings new therapeutic target next generation sequencing novel prevent research study success trait

项目摘要

Project Summary/Abstract 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 neovascularization 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 in influencing disease. We and others have conducted experiments to identify genetic loci for refractive error in families using microsatellite markers followed by single nucleotide polymorphisms for fine mapping. In this proposal, we will extend our previous work to facilitate the discovery of additional genes involved in refractive error. This work will take advantage of already acquired DNA samples from thousands of well-characterized patients. Our work has the potential of discovering novel sequences and genes that interact with environmental risk factors, as well as categories of sequence elements that play a primary or modifying role in refractive error.

项目概要/摘要屈光不正是世界上最常见的眼部疾病，其公众健康和经济影响相当大。美国人口的治疗屈光不正的费用是青光眼的两倍，是 AMD 或 AMD 的 10 倍糖尿病视网膜病变是美国公共卫生系统的主要负担。当前的屈光不正的治疗并不针对继发性并发症。这样的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；视力低下的青光眼患病率为 4.2% 近视，中度至高度近视的眼睛为 4.4%，而中高度近视的眼睛为 1.5% 没有近视。患有远视的人患眼病的可能性高出 40% 高血压患者高于正视患者。眼睛视网膜脱离增加患有屈光不正；近视眼视网膜脱离的风险增加4-10倍。最后，轻度近视的脉络膜新生血管形成风险增加了 2 倍重度近视可达9倍。目前的治疗方法不能预防眼部并发症继发于屈光不正，因为它们的目的不是阻止屈光不正的进展屈光不正。先前尝试用光学控制屈光不正的进展药物方法取得的成功有限。有大量证据表明远视具有重要的遗传因素和近视。如果我们能够识别出与这些疾病相关的基因，那么我们就能够识别出与这些疾病相关的基因。未知的疾病机制，开发这些机制的动物模型，使用这些模型来开发和测试新的治疗方法，确定这些模型之间的相互作用具有可改变的环境风险因素的基因，并在早期就对人们进行治疗防止病程继发并发症。主要挑战之一现在生物医学研究面临的是特定疾病机制的发现是表现出复杂遗传模式的遗传性疾病的基础。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的情况类似，序列变异在屈光不正中起着重要作用疾病。基因技术和生物信息学的进步使得进行实验，检查大规模的数十万个遗传变异个体的数量并确定他们的位置和影响的重要性疾病。我们和其他人进行了实验来识别基因位点使用微卫星标记和单核苷酸检测家庭屈光不正用于精细映射的多态性。在本提案中，我们将把之前的工作扩展到促进发现与屈光不正有关的其他基因。这项工作将需要已从数千个经过充分表征的 DNA 样本中获取的优势患者。我们的工作有可能发现新的序列和基因与环境风险因素以及序列元素类别相互作用在屈光不正中起主要或改变作用。