Age-related macular degeneration (AMD) is recognized as the leading cause of blindness in the United States. It affects nearly 1.5 million older Americans and causes loss of vision in more than 7 percent of individuals over 75 years of age. Currently, there are no established means of preventing AMD. The only proven effective treatment, laser photocoagulation, is successful in only a small proportion of cases. While the etiology of AMD is unknown, there is considerable evidence implicating a strong genetic component for the disease. Advances in genomic screening and analysis methodologies make a direct genetic approach to the etiology, pathophysiology, and ultimate therapy of AMD viable. Recent successes with other complex traits, which share genetic and epidemiological similarities with AMD, support the idea that identification of genetic loci responsible for AMD is an achievable goal. The long-term objectives of this project are to identify genes responsible for AMD, develop diagnostic tools to identify patients at risk of developing the disease, and to understand its molecular pathophysiology. This understanding will allow the development of preventive measures and improved methods of treatment. The immediate goal of this research proposal is to map genetic loci cosegregating with AMD in a number of affected families. We will employ both parametric and several nonparametric linkage analysis methods. To achieve these goals, we propose to: 1) Continue to collect additional kindreds containing multiple affected living members; 2) Complete genome-wide screening of AMD families, beginning with a set of candidate loci; 3) Fine-map loci suggestive of linkage and conduct detailed multi- point parametric and nonparametric linkage analysis; and 4) Refine identified loci and begin studies to identify the specific genetic defects responsible for AMD in these families.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012203-05
Application #
6524947
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Chin, Hemin R
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
5
Fiscal Year
2002
Total Cost
$356,383
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Klein, Michael L; Ferris 3rd, Frederick L; Francis, Peter J et al. (2010) Progression of geographic atrophy and genotype in age-related macular degeneration. Ophthalmology 117:1554-9, 1559.e1
Francis, P J; Hamon, S C; Ott, J et al. (2009) Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss. J Med Genet 46:300-7
SanGiovanni, John Paul; Arking, Dan E; Iyengar, Sudha K et al. (2009) Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS One 4:e5508
Francis, Peter J; Zhang, Hong; Dewan, Andrew et al. (2008) Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. Mol Vis 14:1395-400
Francis, Peter J; Appukuttan, Binoy; Simmons, Emily et al. (2008) Rhesus monkeys and humans share common susceptibility genes for age-related macular disease. Hum Mol Genet 17:2673-80
Klein, Michael L; Francis, Peter J; Rosner, Bernard et al. (2008) CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration. Ophthalmology 115:1019-25
Francis, Peter J; Schultz, Dennis W; Hamon, Sara et al. (2007) Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration. PLoS One 2:e1197
Seddon, Johanna M; Francis, Peter J; George, Sarah et al. (2007) Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA 297:1793-800
Barral, Sandra; Francis, Peter J; Schultz, Dennis W et al. (2006) Expanded genome scan in extended families with age-related macular degeneration. Invest Ophthalmol Vis Sci 47:5453-9
Seddon, Johanna M; George, Sarah; Rosner, Bernard et al. (2006) CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Hum Hered 61:157-65

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