The primary goals of this project are first to develop and validate electronic algorithms, to accurately identify cases and controls for each ophthalmic phenotype, and to conduct genome wide association studies that advance our understanding of these disease states and their treatment. The next goal will be to translate clinically meaningful results into clinical practice. The Marshfield Clinic is an ideal setting for translational research, in part because an internally-developed electronic health record facilitates timely incorporation of research results with necessary decision support tools for health care providers.
Specific aims i nclude: 1. Develop and validate electronic algorithms for ophthalmic conditions and efficacy of medical therapy for ophthalmic conditions and implement other phenotype algorithms developed across the eMERGE network.
Aim 1 a. Develop and validate electronic algorithms for ocular hypertension/glaucoma, intraocular pressure (lOP) response to lOP lowering medications, AMD, response to AMD treatment, tear film insufficiency, response to artificial tears used to treat tear film insufficiency Aim lb. Implement electronic algorithms for phenotypes developed at the other eMERGE sites and share data with the other sites. 2. Leverage GWAS data available for nearly 5000 research subjects aged 50 years and older in Marshfield and an additional 20-25,000 subjects throughout the eMERGE network to undertake genetic discoveries for ophthalmic conditions and ophthalmic pharmacogenetics. Statistical analyses will include traditional GWAS using the SNP data, analysis of copy number variant (CNV) data, and gene/environment analyses. 3. Undertake consultation activities with the general community and clinicians related to the incorporation of GWAS results into electronic health records to inform health care decisions.
Aim 3 a. Conduct focus group discussion with ophthalmologists related to genetic-based prescribing Aim 3b. Meet with the PMRP Community Advisory Group to discuss potential reconsent of study subjects to allow the sharing of genetic data Aim 3c. Communicate with the entire PMRP cohort about return of results and study progress Aim 3d. Contact all subjects with GWAS data to obtain consent to share their GWAS data with themselves and/or their health care providers, based on the results of the consultation efforts Aim 3e. Incorporate clinically relevant GWAS data in the EMRs for ophthalmologists and optometrists

Public Health Relevance

With the ageing of the population, vision disorders are becoming more common, impacting quality of life and health care costs. The proposed project will identify gene/environment predictors of glaucoma/ocular hypertension (the second leading cause of blindness), age-related macular degeneration (the leading cause of blindness in the elderly) and dry eye, as well as genetic predictors of response to medical therapy for these conditions. Use of clinically meaningful GWAS data could save sight and health care costs.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1-HGR-N (M1))
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Li, Rongling
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Essentia Institute of Rural Health
United States
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