Genetic Epidemiology of Refractive Error

项目摘要/摘要 屈光不正是世界上最常见的眼病，其公众 对健康和经济的影响是相当大的。美国人口因此而受到的待遇 屈光不正的费用是青光眼的两倍，是AMD或 糖尿病视网膜病变是美国公共卫生系统的主要负担。当前 屈光不正的治疗不针对继发性并发症。是这样的 并发症包括脉络膜新生血管、视网膜脱离和青光眼。 青光眼是近视的一种并发症；低视力者青光眼的患病率为4.2%。 近视和4.4%的中高度近视与1.5%的近视 没有近视。远视患者患眼病的可能性高出40% 高血压比那些正视的人要高。眼部视网膜脱离增多 屈光不正时，近视眼发生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风险增加了2倍。 对于重度近视，则为9倍。目前的治疗方法不能预防眼部并发症。 屈光不正是次要的，因为它们不是针对阻止进展的 屈光不正。以前用光学方法控制屈光不正进展的尝试 而药物方法也取得了有限的成功。 有大量证据表明远视的重要遗传成分 还有近视。如果一个人能够识别与这些疾病有关的基因，就可以识别 意想不到的疾病机制，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，确定它们之间的相互作用 带有可改变的环境风险因素的基因，并在很早的时候治疗人们 以防止继发性并发症的发生。主要挑战之一是 现在面临的生物医学研究是发现特定的疾病机制， 表现出复杂遗传模式的可遗传疾病是其基础。这包括 复杂的眼部疾病，如屈光不正。一个吸引人的假设是 与其他复合体一样，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我们有可能 进行大量检测数十万种基因变异的实验 确定个人数量，并确定其在影响中的位置和重要性 疾病。我们和其他人已经进行了实验，以确定 使用微卫星标记和单核苷酸的家系中的屈光不正 用于精细作图的多态。在这项提案中，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 已经从数千个特征良好的DNA样本中获取DNA样本的优势 病人。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的类别相互作用 在屈光不正中扮演主要或矫正的角色。

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.