Age-related macular degeneration (AMD) is the most common cause of severe vision loss among individuals over age 50 in the U.S. The socioeconomic impact is considerable and will only get worse as the U.S. population ages. Unfortunately, treatment options remain limited because the etiology of this devastating disease is complex and largely unknown. Considerable evidence implicates a combination of genetic and environmental factors in the pathogenesis of AMD. We have demonstrated that underlying genetic variation is critical to the development of AMD and hypothesize interactions with environmental factors may trigger both the development and progression of the disease. Numerous independent genomic screens, including our collaborative effort with the University of Pittsburgh, have consistently implicated chromosomes 1,10, and 16. Thus it is time to begin detailed mapping and /or gene identification studies in these high priority regions of interest. Our recent identification of the T1277C polymorphism in CFH on chromosome 1 as an AMD susceptibility allele requires detailed follow-up and shows the feasibility of this approach in identifying the genes on chromosomes 10 and 16. Even with this exciting CFH result, the number of genes to be interrogated on chromodomes 10 and 16 is large. To further prioritize within this gene pool, we will invoke the genomic convergence, which combines genetic linkage results, allelic/genotypic/haplotypic association results, and gene expression results to prioritize and test candidate genes for their involvement in AMD.
Our specific aims are: to extend our current patient and family data set to include a data set of 1000 cases and 1000 controls; to perform a detailed examination of CFH and other genes in the Regulator of Complement Activity complex on chromosome 1; to perform detailed association analyses across the critical regions of chromosomes 10 and 16, similar to our successful approach on chromosome 1; to generate gene expression data from RPE cells from patients and controls focused specifically on all the genes lying within the chromosome 10 and 16 regions; test candidate genes for association with AMD; and to test for gene-gene and gene-environmental interactions incorporating already identified risk factors such as smoking and the apolipoprotein E (APOE) polymorphisms. The knowledge derived from this study will further our understanding of AMD and will be crucial for future studies to develop and test interventions. ? ?

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-F (03))
Program Officer
Chin, Hemin R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Sardell, Rebecca J; Persad, Patrice J; Pan, Samuel S et al. (2016) Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus. Invest Ophthalmol Vis Sci 57:6107-6115
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:
Hoffman, Joshua D; van Grinsven, Mark J J P; Li, Chun et al. (2016) Genetic Association Analysis of Drusen Progression. Invest Ophthalmol Vis Sci 57:2225-31
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Sardell, Rebecca J; Bailey, Jessica N Cooke; Courtenay, Monique D et al. (2016) Whole exome sequencing of extreme age-related macular degeneration phenotypes. Mol Vis 22:1062-76
Kovach, Jaclyn L; Schwartz, Stephen G; Agarwal, Anita et al. (2016) The Relationship Between Reticular Pseudodrusen and Severity of AMD. Ophthalmology 123:921-3
Butkiewicz, Mariusz; Cooke Bailey, Jessica N; Frase, Alex et al. (2016) Pathway analysis by randomization incorporating structure-PARIS: an update. Bioinformatics 32:2361-3
Li, Zheng; Allingham, R Rand; Nakano, Masakazu et al. (2015) A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet 24:3880-92

Showing the most recent 10 out of 52 publications