This proposal describes a population-based cohort study aimed at describing the family aggregation of age-related cataracts, visual function, intra-ocular pressure, and systemic characteristics of aging, cross-sectionally and longitudinally The population resides in Beaver Dam, Wisconsin. Subjects were 43-86 years of age at the first examination in 1988-90 Standardized protocols for interviews, examination, blood tests, and ocular photography and grading were performed at first examination and two follow-up examinations in 1993-95 and 1998-2000. Within the baseline population (n equals 4,926) we identified 587 sibling groups composed of 1,403 persons. Study participants have had standardized examinations at the three examination cycles. Information has been collected regarding cataract, other age-related eye diseases, medical conditions, medication usage; blood pressures, height and weight have been measured, as have several blood parameters baseline. At the follow-up visits, other measures of frailty (estimated by hand grip strength, slower timed walk, decrease peak expiratory flow) have been added to the protocol. Mortality has been carefully monitored and death certificate information has been obtained. We will investigate whether changes in cataract, as well as other ocular and systemic factors, aggregate in families and whether families that display greater progression of cataracts are at greater risk of systemic morbidity, frailty and mortali1y. During the course of the study, we have had follow-up interviews during which we have become aware of about 400 avuncular, parent and cousin relations in the community. We will complete our family pedigree information prior to the beginning of this grant. We propose extensive family aggregation analyses using generalized estimating equations and, when appropriate, commingling and segregation analyses. This grant will capitalize on data previously collected from grants funded by the National Eye Institute. We currently have no funds to support the proposed analyses. We believe this project offers the possibility of examining important hypotheses in a large group of families in a population-based framework.
| Sivakumaran, Theru A; Igo Jr, Robert P; Kidd, Jeffrey M et al. (2011) A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration. PLoS One 6:e25598 |
| Kopplin, L J; Igo Jr, R P; Wang, Y et al. (2010) Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. Genes Immun 11:609-21 |
| Jun, Gyungah; Guo, Hong; Klein, Barbara E K et al. (2009) EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genet 5:e1000584 |
| Chang, Bo; Mandal, Md Nawajes A; Chavali, Venkata R M et al. (2008) Age-related retinal degeneration (arrd2) in a novel mouse model due to a nonsense mutation in the Mdm1 gene. Hum Mol Genet 17:3929-41 |
| Thompson, Cheryl L; Jun, Gyungah; Klein, Barbara E K et al. (2007) Genetics of pigment changes and geographic atrophy. Invest Ophthalmol Vis Sci 48:3005-13 |
| Thompson, Cheryl L; Klein, Barbara E K; Klein, Ronald et al. (2007) Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. Hum Mol Genet 16:2135-48 |
| Klein, Ronald; Klein, Barbara Eden Kobrin (2006) The epidemiology of eye disease: from glycemia to genetics: the Friedenwald Lecture. Invest Ophthalmol Vis Sci 47:1746-53 |
| Jun, Gyungah; Klein, Barbara E K; Klein, Ronald et al. (2005) Genome-wide analyses demonstrate novel loci that predispose to drusen formation. Invest Ophthalmol Vis Sci 46:3081-8 |
| Klein, Alison P; Duggal, Priya; Lee, Kristine E et al. (2005) Support for polygenic influences on ocular refractive error. Invest Ophthalmol Vis Sci 46:442-6 |
| Klein, Alison P; Duggal, Priya; Lee, Kristine E et al. (2005) Polygenic effects and cigarette smoking account for a portion of the familial aggregation of nuclear sclerosis. Am J Epidemiol 161:707-13 |
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