Linkage Studies of Quantitative Ocular Traits

描述（由申请人提供）：本提案描述了一项定量眼性状的遗传流行病学研究。每个人都有这些眼部特征，这些特征与随后的疾病发展有关，在某些情况下可能导致视力损害。我们拟研究的特征包括眼内压和视盘杯直径，这可能与青光眼的发展有关；核硬化，一个持续一生的过程，在一些人身上，会导致明显的核性白内障；当屈光不正两侧大于1屈光度时，通常需要使用眼镜或镜片矫正以获得最佳视力，并可能限制职业机会并影响生活质量；视网膜血管直径，与血压有关；冠心病和中风。这些数量性状的值倾向于在家族中聚集，统计分析表明这些性状可能有遗传决定因素。海狸坝眼科研究（n=4926）是一项基于人群的年龄相关眼病研究。所有程序、调查问卷、晶状体和视网膜摄影以及这些照片的分级程序都是根据编纂的规程进行的。在1988-1990年间，共有602个家庭参加了基线检查。在这些家庭中，有2291人的血液标本被采集并冷冻在-80摄氏度。建议对这些人的血液进行全基因组扫描的遗传连锁分析，以确定定量眼部性状的遗传相关性。遗传疾病研究中心已经完成了全基因组扫描。需要支持来协调差异、检查错误，并执行基本的统计分析和联系分析。

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.