Through genetic analysis of case-control cohorts there has been remarkable progress in identifying genes for Age-Related Macular Degeneration. Most of these identifications have been accomplished through the interrogation of common variants. We will initiate the identification of rare variants in a founder population, the Amish, and use the whole exome chip to assess the association of Age-related Macular Degeneration with coding variants. We will further refine the Age-Related Macular Degeneration phenotype through the use of modern imaging, the OCT, to visualize the early anatomic signs of Age-Related Macular Degeneration. We hypothesize there are endophenotypes associated with specific genotypes that can be used to determine Age-related Macular Degeneration progression. These endophenotypes are hypothesized to be influenced by a combination of common and rare variants. Following the completion of these Aims, we will have phenotypically defined the early signs of Age-Related Macular Degeneration aiding our understanding of this disease. Moreover, we will relate these signs to genotypes to define the role of genetics in the progression of Age-Related Macular Degeneration and a new risk profile incorporating genotypic information.

Public Health Relevance

Identification of the genes for Age-related Macular Degeneration has made remarkable progress. Still, there is a need to discover more genes that can inform additional biological pathways beyond the complement system. There is also an urgency to identify early anatomical defects that can be used as biomarkers for progression of disease. This proposal aims to define the early clinical signs of Age-related Macular Degeneration and identify rare variants with large impact on disease progression to both improve patient care and our overall understanding of Age-related Macular Degeneration.

National Institute of Health (NIH)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZEY1)
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Shen, Grace L
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University of Pennsylvania
Schools of Medicine
United States
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Diniz, B; Rodger, D C; Chavali, V R et al. (2015) Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population. Eye (Lond) 29:272-9
Fritsche, Lars G; Fariss, Robert N; Stambolian, Dwight et al. (2014) Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet 15:151-71