Genetic Determinants of Optic Nerve Head Structure

描述(申请人提供)：这项研究项目使用新颖和创新的策略，通过计算来开发高保真视神经头(ONH)结构的内表型。这些计算表型可以量化ONH结构，并将测量每幅图像，跨越几个特征良好的队列(OHTS、AREDS、爱荷华州和鹿特丹)的多种成像模式。我们将使用遗传归因策略来最大限度地利用我们的能力来识别真正的关联，并最终识别我们计算的ONH结构内表型的原因变异。将采用系统生物学的方法来确定相关基因座和基因之间的生物和/或功能关系。这项研究的最终目标是确定生物标志物和/或遗传风险因素，以准确预测：(1)初级视神经头(ONH)结构(即在年龄或疾病相关变化之前)，(2)ONH结构的变化，以及(3)不可逆性青光眼视神经损害发生前的发展。这些结果将提高青光眼初始诊断的特异性和敏感性，使临床医生能够确定这种疾病造成的ONH结构变化的比例，而不是初级ONH结构的正常变化。这反过来将允许应用当前可用和有效的 在视力丧失之前开始治疗。

DESCRIPTION (provided by applicant): This research project uses novel and innovative strategies to develop high-fidelity optic nerve head (ONH) structure endophenotypes computationally. These computational phenotypes allow quantification of ONH structure, and will be measured for each image, spanning multiple imaging modalities from several well-characterized cohorts (OHTS, AREDS, IOWA, and Rotterdam). We will use a genetic imputation strategy to maximize our power to identify bona fide associations, and ultimately the causative variations, for our computational ONH structure endophenotypes. A systems biology approach will be employed to identify biological and/or functional relationships among the associated loci and genes. The ultimate goal of this research proposal is identify biomarkers and/or genetic risk factors that accurately predict: (1) primary optic nerve head (ONH) structure (i.e. before age- or disease-related changes), (2) changes in ONH structure, and (3) the development of irreversible glaucomatous optic nerve damage before it occurs. These outcomes will improve the specificity and sensitivity of initial diagnosis of glaucoma, allowing clinicians to determine the proportion o ONH structure change that is damage from this disease, as opposed to normal variations in primary ONH structure. This in turn will allow the application of currently available and effective therapies to be instituted before vision is lost.