We hypothesize that underlying susceptibility gene (s) are critical to the development of age-related macular degeneration (AMD) and that they most likely interact with environmental factors to trigger the development and progression of this disease. We propose a multi-pronged approach to the identification of susceptibility gene(s) for age-related macular degeneration (AMD). During the initial grant period we developed a large genetic AMD database including large families and multiplex families with affected sib-pairs, and have identified several areas of genetic linkage to pursue. During the next grant period, we propose a multipronged approach to build upon this database, with the goal of finding the gene or genes associated with AMD susceptibility. We will use family-based and population-based case-control association studies, combined with an expanded genome-wide sib-pair study for this project. Single nucleotide polymorphisms in high priority positional or functional AMD candidate loci will be genotyped for the association studies and linkage disequilibrium and transmission disequilibrium tests will be performed. Sib-pair linkage analysis using both quantitative and qualitative traits on the expanded genome-wide scan will be completed. We will collect family history and risk factor data and conduct studies examining these risk factors for AMD. These data will provide important information to analyze the influence of environmental factors as information about specific genetic factors involved in the disease is identified. This study should provide important new information about the etiology of AMD which is the leading cause of irreversible blindness among elderly individuals worldwide, so that preventative or treatment measures can be developed. ? ? ? ?

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZEY1-VSN (09))
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Chin, Hemin R
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Massachusetts Eye and Ear Infirmary
United States
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Seddon, Johanna M; Ferrara, Daniela (2017) Rare Genetic Variants in Age-Related Macular Degeneration. JAMA Ophthalmol 135:1045-1046
Seddon, Johanna M (2017) Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions - The Weisenfeld Award Lecture. Invest Ophthalmol Vis Sci 58:6513-6528
Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard et al. (2017) Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 58:4569-4578
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Yu, Yi; Wagner, Erin K; Souied, Eric H et al. (2016) Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration†. Hum Mol Genet 25:5276-5285
Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard et al. (2016) Dietary folate, B vitamins, genetic susceptibility and progression to advanced nonexudative age-related macular degeneration with geographic atrophy: a prospective cohort study. Am J Clin Nutr 103:1135-44
Shah, Anjali R; Williams, Steven; Baumal, Caroline R et al. (2016) Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration. Am J Ophthalmol 163:154-166.e8

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