Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study

The purpose of the POAAGG study is to investigate the genetic architecture of primary open-angle glaucoma (POAG) in African Americans. This population is up to eight times more likely to develop glaucoma than non-Hispanic whites, yet no large-scale genetics studies have specifically addressed this ethnic group. The POAAGG study aims to enroll 7765 patients, consisting of a discovery cohort of 5500 subjects (2000 cases and 3500 controls) and a validation cohort of 2265 subjects (1000 cases and 1265 controls). The study population consists of self-identified blacks (African Americans, African descent, or African Caribbean), 35 years or older, identified from the Philadelphia region. Subjects are recruited from the Scheie Eye Institute and its research sites in Philadelphia, PA, as well as from the Penn Medicine Biobank. Fellowship-trained glaucoma specialists classify each subject as a case, control, or glaucoma suspect based on specified criteria. As of 02/01/2017, a total of 8187 subjects have been recruited to the POAAGG study, including 2522 cases, 4545 controls, and 1120 suspects. A comprehensive genetic analysis of POAG, including a genome-wide association analysis, is currently underway. The GWAS was conducted on the Illumina Infinium Multi Ethnic Genotyping Array (MEGA), which contained custom content tailored to POAG and African Americans. A comprehensive genetic analysis of quantitative traits associated with POAG is also in progress. Over 90% of cases have full phenotypic information, including intraocular pressure, cup-to-disc ratio, central corneal thickness, retinal nerve fiber layer thickness, visual acuity, and visual fields.]]>
0000Inclusion criteria for POAAGG subjects includes age over 35 years and self-identification as Black (African-American, African descent, or African Caribbean). Exclusion criteria include a history of narrow angle, closed angle, neovascular, mixed mechanism, or pseudoexfoliation glaucoma; history of glaucoma secondary to eye surgery or secondary to severe ocular trauma; history of iritis, uveitis, or iridocyclitis; presence of Grave's disease with ocular manifestations, vascular occlusion causing neovascularization of the iris, optic nerve atrophy from other diagnoses, or advanced proliferative diabetic retinopathy. POAG cases were defined as having an open iridocorneal angle and: (1) characteristic glaucomatous optic nerve findings in one or both eyes consisting of at least one of the following: notching, neuroretinal rim thinning, excavation, or a nerve fiber layer defect; (2) characteristic visual field defects on two consecutive reliable visual field tests in at least one eye, which were consistent with the observed optic nerve defects in that eye, as determined by fellowship-trained glaucoma specialists; and (3) all secondary causes of glaucoma excluded. Normal controls were defined as subjects older than 35, without: (1) high myopia (greater than -8.00 diopters); (2) high presbyopia (+8.00 diopters); (3) abnormal visual field; (4) IOP greater than 21 mmHg; (5) neuroretinal rim thinning, excavation, notching or nerve fiber layer defects; (6) optic nerves asymmetry; or (7) a cup-to-disc ratio difference between eyes greater than 0.2.]]>
July 2010: Enrollment for discovery cohort of POAAGG study begins. October 2013: First manuscript for POAAGG study published (Collins et al., 2013). March 2014: Funding from National Eye Institute received. August 2014: POAAGG study begins outreach efforts in Philadelphia community, bringing a mobile van with glaucoma screening equipment to at-risk areas of city. October 2014: POAAGG study begins to offer free glaucoma screenings at Scheie Eye Institute, which are advertised in local subway. November 2014: POAAGG study switches primary method of DNA sample collection from blood to saliva samples, after evaluating concordance of genotyping from two methods (Gudiseva et al, 2016). May and July 2015: POAAGG study expands enrollment from three UPenn sites (Scheie Eye Institute, Perelman Center for Advanced Medicine, Mercy Fitzgerald Hospital) to two new external sites (Windell Murphy, MD and Ophthalmology Department at the Lewis Katz School of Medicine at Temple University). September 2015: POAAGG study incorporates DNA from 1780 African American patients from the Penn Medicine Biobank into cohort. February 2016: Enrollment for validation cohort of POAAGG study begins. July 2016: Genotyping of discovery cohort (n=5520) completed on Illumina Infinium Multi Ethnic Genotyping Array (MEGA) GWAS/EWAS analysis of POAG and related phenotypes. August 2016-present: GWAS association analysis of discovery cohort underway with New York Genome Center, as well as Jason Moore and Bioinformatics Core at UPenn. ]]>