Linkage Studies of Quantitative Ocular Traits

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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.