Genetic Epidemiology of Refractive Error

项目总结/摘要 屈光不正是世界上最常见的眼部疾病，其公众 健康和经济影响是相当大。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。电流 屈光不正的治疗并不针对继发性并发症。等 并发症包括脉络膜新生血管形成、视网膜脱离和青光眼。 青光眼是近视的一种并发症;青光眼的患病率为4.2%， 4.4%的眼睛患有中度至高度近视，而1.5%的眼睛患有中度至高度近视。 没有近视。患有远视的人有40%的可能性会发展成眼睛 高血压的人比正视眼的人多。视网膜脱离的症状有哪些？ 伴有屈光不正;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 高度近视的近视度数为9倍。目前的治疗不能预防眼部并发症 继发于屈光不正，因为它们的目标不是阻止 屈光不正先前尝试用光学仪器控制屈光不正的进展 和药物治疗的效果有限。 有大量的证据表明，远视有显著的遗传成分 和近视。如果人们能识别出这些疾病中的基因， 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，确定这些方法之间的相互作用， 具有可改变的环境风险因素的基因，并在 预防继发性并发症。的主要挑战之一 现在生物医学研究面临的是发现特定的疾病机制， 是遗传性疾病的基础，这些疾病表现出复杂的遗传模式。这包括 复杂的眼部疾病，如屈光不正。一个吸引人的假设是， 序列变异在屈光不正中起着重要作用，类似于其他复杂的 疾病遗传技术和生物信息学的进步使我们有可能 进行大量的实验， 个人的数量，并确定他们的位置和影响的重要性， 疾病我们和其他人已经进行了实验，以确定遗传位点， 用微卫星标记后接单核苷酸检测屈光不正家系 多态性用于精细作图。在本提案中，我们将把以前的工作扩展到 有助于发现与屈光不正有关的其他基因。这项工作将需要 从数千个已被充分表征的DNA样本中获得的优势 患者我们的工作有可能发现新的序列和基因， 与环境风险因素相互作用，以及 在屈光不正中起主要或修正作用。

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.