Linkage Studies of Quantitative Ocular Traits

描述(由申请人提供)：这项提案描述了一项关于眼部数量性状的遗传流行病学研究。这些在每个人身上都会发生的眼睛特征，与随后的疾病发展有关，在某些情况下，这些疾病可能会导致视力障碍。我们建议研究的特征包括眼压、视盘和视杯直径，这可能与青光眼的发展有关；核硬化，这是一种持续一生的过程，在某些人中，会导致明显的核性白内障；屈光，当正视两侧超过一个屈光度时，通常需要使用眼镜或镜片矫正才能获得最佳视力，可能会限制职业机会并影响生活质量；视网膜血管直径，已与血压、冠心病和中风有关。这些数量性状的值往往聚集在家系中，统计分析表明，这些性状可能有遗传决定因素。海狸水坝眼科研究(n=4926)是一项以人群为基础的年龄相关眼病研究。所有的程序、问卷、晶状体和视网膜的摄影以及这些照片的分级程序都是按照编撰的方案进行的。有602个家庭参加了1988-1990年的基线检查。在这些家庭中，有2291人的血液样本被采集并在零下80摄氏度冷冻。建议使用对这些人的血液进行全基因组扫描的遗传连锁分析来确定数量眼部特征的遗传相关性。遗传病研究中心已经完成了全基因组扫描。需要支助来协调差异、检查错误以及执行基本的统计分析和联系分析。 这项研究充分利用了所有未被选入海狸水坝眼科研究的研究对象的表型信息，包括疾病状况、大量的家庭成员以及支持遗传原因的强有力的统计遗传学证据。对这些特征的研究有望确定疾病发展之前存在的风险因素的遗传相关性。基于这项研究结果的预防战略可以旨在阻止或减少发生重大疾病的可能性。随后计划对基因组中感兴趣的区域进行精细绘制。

DESCRIPTION (provided by applicant): This proposal describes a genetic epidemiologic study of quantitative ocular traits. These ocular traits, which occur in everyone, are associated with the subsequent development of diseases which in some cases may lead to visual impairment. The traits we propose to study include intraocular pressure and optic disc and cup diameters, which may be related to the development of glaucoma; nuclear sclerosis, a process that continues throughout life and in some people, results in an overt nuclear cataract; refraction which, when greater than about one diopter on either side of emmetropia, often requires the use of spectacles or lens correction for best vision, and may limit professional opportunities and influence quality of life; and retinal vessel diameters, which has been associated with blood pressure; coronary heart disease, and stroke. Values of these quantitative traits tend to aggregate in families and statistical analyses suggest that there are likely to be genetic determinants of these traits. The Beaver Dam Eye Study (n=4926), is a population-based study of age-related eye disease. All procedures, questionnaires, photography of the lens and retina and grading procedures of those photographs were done according to codified protocols. There were 602 families that participated in the baseline examination in 1988-1990. There were 2291 persons in these families from whom blood specimens were obtained and frozen at -80 degrees C. Genetic linkage analyses using a genome-wide scan on blood from these persons is proposed to determine genetic correlates of quantitative ocular traits. Genome-wide scans have been completed at the Center for Inherited Disease Research. Support is needed to reconcile discrepancies, check errors, and perform basic statistical analyses and linkage analyses. This study takes advantage of the availability of thorough information on phenotypes of all study subjects who were not selected for inclusion in the Beaver Dam Eye Study by disease status, the large number of family members, and the strong statistical genetic evidence in favor of genetic causes. Studying these traits holds promise of determining genetic correlates of risk factors which are present prior to the development of disease. Preventive strategies based on results of this study could be aimed at deterring or diminishing the probability of development of significant diseases. Subsequent follow-up with fine mapping of areas of interest in the genome is planned.