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)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Shen, Grace L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
Hughes, Anne E; Bridgett, Stephen; Meng, Weihua et al. (2016) Sequence and Expression of Complement Factor H Gene Cluster Variants and Their Roles in Age-Related Macular Degeneration Risk. Invest Ophthalmol Vis Sci 57:2763-9
Cooke Bailey, Jessica N; Hoffman, Joshua D; Sardell, Rebecca J et al. (2016) The Application of Genetic Risk Scores in Age-Related Macular Degeneration: A Review. J Clin Med 5:
Sardell, Rebecca J; Nittala, Muneeswar G; Adams, Larry D et al. (2016) Heritability of Choroidal Thickness in the Amish. Ophthalmology 123:2537-2544
Tian, Lifeng; Kazmierkiewicz, Krista L; Bowman, Anita S et al. (2015) Transcriptome of the human retina, retinal pigmented epithelium and choroid. Genomics 105:253-64
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
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) 29:300
Chavali, Venkata Ramana Murthy; Diniz, Bruno; Huang, Jiayan et al. (2015) Association of OCT derived drusen measurements with AMD associated-genotypic SNPs in Amish population. J Clin Med 4:304-317
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
Cooke Bailey, Jessica N; Pericak-Vance, Margaret A; Haines, Jonathan L (2014) Genome-wide association studies: getting to pathogenesis, the role of inflammation/complement in age-related macular degeneration. Cold Spring Harb Perspect Med 4:a017186