Primary open angle glaucoma (POAG) is a significant cause of blindness worldwide. The etiology of POAG is poorly understood and primary prevention is not possible. Current treatments can slow but do not cure this progressive neuropathy. The overall goal of our research is to elucidate the pathogenesis of primary open-angle glaucoma (POAG) making it possible to implement effective screening and prevention strategies and to develop novel therapies. While POAG has a significant heritability, recent genome-wide association studies using moderate sample sizes have only identified a few POAG-related genes with modest effect sizes. These results suggest that large datasets with well-defined phenotypes are needed to fully delineate the genetic architecture of POAG. This proposal will efficiently use existing datasets to create a large sample useful for investigation o genetic determinants of POAG, with a primary focus of identifying genes contributing to the POAG-related quantitative endophenotype, cup-to-disc ratio (CDR). Emerging data suggests that CDR, even when subjectively ascertained, is an important outcome providing valuable insights into the pathogenesis of POAG. Previously we formed two collaborative consortia contributing 3,517 POAG cases and 3,631 controls for GWA studies, the NEIGHBOR consortium (NEI Glaucoma Human genetic collaboration) and the GLAUGEN study (Glaucoma Genetics). The immediate goals of this proposal are: 1) expand the NEIGHBOR and GLAUGEN consortia to create the NEIGHBORHOOD (NEIGHBOR Heritable Overall Operational Database) consortium and database, which will include harmonized genotype and phenotype data for a total of 4,652 POAG cases, 16,909 subjects with CDR and 42,486 controls~ and, 2) use this enhanced dataset to perform meta-analyses to identify novel genes influencing CDR, as well as genes that contribute to POAG. Additionally, this proposal will form the basis of future studies of other POAG related traits and gene-gene and gene-environment interactions for CDR and POAG.

Public Health Relevance

Primary open angle glaucoma (POAG) causes permanent loss of vision and is a condition of public health significance worldwide, affecting millions of people. The etiology of POAG is poorly understood and effective means of primary prevention and curative therapies are not available. In this proposal, our collaborative consortium will develop an operational database housing phenotype and genotype information for over 4600 POAG cases, 16,000 individuals with data for the heritable POAG endophenotype cup-to-disc ratio (CDR), and 42,000 controls that can be used to identify risk factors for POAG with the ultimate goal of elucidating the molecular pathogenesis of POAG making it possible to implement effective screening and prevention strategies and to develop novel therapies.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZEY1-VSN (01))
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Agarwal, Neeraj
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Massachusetts Eye and Ear Infirmary
United States
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Kang, Jae H; Wu, Juan; Cho, Eunyoung et al. (2016) Contribution of the Nurses' Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma. Am J Public Health 106:1684-9
Bailey, Jessica N Cooke; Loomis, Stephanie J; Kang, Jae H et al. (2016) Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet 48:189-94
Liu, Yutao; Bailey, Jessica Cooke; Helwa, Inas et al. (2016) A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium. Invest Ophthalmol Vis Sci 57:3974-81
(2016) Erratum. Invest Ophthalmol Vis Sci 57:4528
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Butkiewicz, Mariusz; Cooke Bailey, Jessica N; Frase, Alex et al. (2016) Pathway analysis by randomization incorporating structure-PARIS: an update. Bioinformatics 32:2361-3
Igo Jr, Robert P; Cooke Bailey, Jessica N; Romm, Jane et al. (2016) Quality Control for the Illumina HumanExome BeadChip. Curr Protoc Hum Genet 90:2.14.1-2.14.16
Khawaja, Anthony P; Cooke Bailey, Jessica N; Kang, Jae Hee et al. (2016) Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses. Invest Ophthalmol Vis Sci 57:5046-5052
Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G et al. (2015) Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology. Genet Epidemiol 39:207-16
Kang, Jae H; Loomis, Stephanie J; Rosner, Bernard A et al. (2015) Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study. Invest Ophthalmol Vis Sci 56:2439-48

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