R01EY032559

Understanding the Clinical Impact of Cumulative Genetic Risk to Glaucoma - Primary Open-Angle Glaucoma (POAG), the most common glaucoma subtype, is a prototypical common complex disease with a strong polygenic component. This proposal is aligned with the NIH Roadmap, leveraging the decade-long effort of gene discovery for POAG into precision medicine approaches that facilitate an early glaucoma diagnosis while outlining strategies to prevent glaucoma-related blindness.

In this study, we propose 3 specific aims.

1) We will assemble all of the common gene variants discovered for POAG over the past decade into a multi-ancestry panel to test whether they predict glaucoma in 4 independent study populations. These populations include the UK Biobank, a health professional case-control study embedded in a population-based sample, and patients from 2 hospital-based biobanks. The total sample size will be over 12,000 POAG cases in approximately 600,286 subjects.

2) Hospital-based biobanks offer an opportunity to contribute precision-based medical knowledge about glaucoma. We will invite 800 patients from two hospital-based biobanks with low and high glaucoma polygenic risk score (PRS) for systematic clinical evaluation. This detailed phenotype-genotype correlation will provide unique insights into glaucoma and will demonstrate the utility of such biobanks to identify previously undiagnosed disease, an unmet need in the field of glaucoma.

3) While a glaucoma PRS is probably the strongest predictor of glaucoma, we anticipate that a considerable number of subjects with high PRS will not demonstrate glaucomatous disease. Conversely, some subjects with low PRS will have glaucoma. We will explore whether genetic variants such as MYOC Q368X and unique environmental factors (dietary nitrate intake from vegetable sources, estrogen exposure duration in women, and dental health status) modify the relation between our PRS and glaucoma in our 4 study populations.

By formulating and applying a multi-ancestral glaucoma PRS to an ethnically-diverse group of subjects, this proposal will highlight the role of a glaucoma genetic informativity panel as a screening tool. This proposal will advance the major objective of promoting POAG to the status of a precision-based medicine discipline. Finally, it will identify specific disease prevention strategies that could be implemented before a diagnosis is made.

Icahn School Of Medicine At Mount Sinai

1) TO SUPPORT EYE AND VISION RESEARCH PROJECTS THAT ADDRESS THE LEADING CAUSES OF BLINDNESS AND IMPAIRED VISION IN THE U.S. THESE INCLUDE RETINAL DISEASES, CORNEAL DISEASES, CATARACT, GLAUCOMA AND OPTIC NEUROPATHIES, STRABISMUS, AMBLYOPIA, AND LOW VISION AND BLINDNESS REHABILITATION. 2) TO INCREASE UNDERSTANDING OF THE NORMAL DEVELOPMENT AND FUNCTION OF THE VISUAL SYSTEM IN ORDER TO BETTER PREVENT, DIAGNOSE, AND TREAT SIGHT-THREATENING CONDITIONS, AND, TO ENHANCE THE REHABILITATION, TRAINING, AND QUALITY OF LIFE OF INDIVIDUALS WHO ARE PARTIALLY-SIGHTED OR BLIND. 3) TO SUPPORT A BROAD PROGRAM OF BASIC VISION RESEARCH THROUGH GRANTS AND COOPERATIVE AGREEMENTS, TO ENCOURAGE HIGH QUALITY CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS, OTHER EPIDEMIOLOGICAL STUDIES, AND HEALTH SERVICES RESEARCH, TO ENCOURAGE RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE SCIENCES RELATED TO VISION, AND TO SPONSOR SCIENTIFIC WORKSHOPS IN HIGH PRIORITY RESEARCH AREAS TO ENCOURAGE EXCHANGE OF INFORMATION AMONG SCIENTISTS. 4) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Eye Institute (NEI) [HHS - NIH]

New York United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 05/31/25 to 03/31/30 and the total obligations have increased 391% from $732,137 to $3,591,952.