Eyes of Africa: The Genetics of Blindness

Principal Investigator:

Scientific Description:

Our Collaborative Center “Eyes of Africa: The Genetics of Blindness” will address the staggering economic, societal, and personal cost of irreversible blindness in Africa. The most common cause of permanent blindness in Africa is primary open angle glaucoma (POAG), which is the dominant type of glaucoma in Sub Saharan Africa (SSA). Multiple studies have found that glaucoma disproportionately affects people of African versus European ancestry. As a disease, POAG constitutes the single greatest cause of permanent blindness in Africa and for this reason is the focus of this proposal. We will identify new susceptibility genes for POAG in order to lay the foundation for novel therapeutic intervention, conduct the Sub-Saharan Africa Glaucoma Laser Trial (SSA-GLT) to identify the optimal approach for early treatment of glaucoma and conduct Targeted Glaucoma Screening in Sub Saharan Africa (TGS-SSA): An approach to identify glaucoma early and increase awareness of glaucoma in Sub-Saharan Africa. Successful completion will identify pre-symptomatic glaucoma for treatment, educate families about the disease, and identify highly penetrant mutations that give rise to early onset glaucoma. Our Collaborative Center will fight blindness in Africa in in multiple complementary and synergistic ways that address critical approaches to identify, treat, and understand POAG in Africa. We will build upon our existing large dataset of genotyped samples, expanding this resource using our extensive group of active subject recruitment sites distributed across Africa. In short, this proposal is designed to provide both an immediate and a long-lasting impact to reduce blindness in Africa.

Updated Aims:
Our Collaborative Center “Eyes of Africa: The Genetics of Blindness” will address the staggering economic, societal, and personal cost of irreversible blindness in Africa. The most common cause of permanent blindness in Africa is primary open angle glaucoma (POAG), which is the dominant type of glaucoma in Sub Saharan Africa (SSA). Multiple studies have found that glaucoma disproportionately affects people of African versus European ancestry. As a disease, POAG constitutes the single greatest cause of permanent blindness in Africa and for this reason is the focus of this proposal
Project 1: We will conduct a Genome Wide Association Study using Primary Open Angle Glaucoma (POAG) case and control blood samples.
Project 2: Collect Multiplex families in which early onset POAG is segregating.
Perform exome sequencing to identify potential Mendelian variants of early onset Glaucoma,
An approach to identify glaucoma early and increase awareness of glaucoma in Sub-Saharan Africa. Successful completion will identify pre-symptomatic glaucoma for treatment. We will educate families about the disease.
Our Collaborative Center will fight blindness in Africa in in multiple complementary and synergistic ways that address critical approaches to identify, treat, and understand POAG in Africa.
We will build upon our existing large data set of genotyped samples, expanding this resource using our extensive group of active subject recruitment sites distributed across Africa. In short, this proposal is designed to provide both an immediate and a long-lasting impact to reduce blindness in Africa.

Data analyses planned for our group

  1. GWAS studies
    • POAG case vs control to identify risk SNPs. We will use single SNP analyses as well as polygenic analyses through the use of genetic risk scores comprised of multiple SNPs.
    • Clinical subgroup analyses vs controls. We will conduct association analyses between Advanced POAG vs control. Advanced POAG can be defined in multiple ways, including visual field cutoff, retina nerve fiber layer thickness cutoff, VCDR cutoff. We will also analyze normotensive glaucoma vs controls and hypertensive glaucoma vs controls.
    • QTL (quantitative trait locus) analysis of a variety of clinical variables including central corneal thickness, intraocular pressure, and variables derived from OCT (ocular coherence tomography). These will include, but not be limited to, these retinal structural measures: optic nerve head area, optic nerve cup area, and retinal nerve fiber layer thickness
  2. PrediXcan analysis to use GWAS data to inpute gene expression patterns. These calculated gene expression data will then be used to prioritize follow-up functional analysis of GWAS loci.
  3. Analysis of phenotype data collected on our study participants. These measurements include OCT measures identified in 1c above, as well as central corneal thickness, visual acuity measures, autorefractor results, etc.
  • Normative measures and descriptions of ocular morphology in various populations, including Igbo, Hausa, Yoruba, and Gambian populations. These data are required for interpretation of our case/control analyses in 2b, but are also interesting in their own right.
  • Structure function analysis of POAG cases and controls. These analyses will use the normative data in 2a to compare to cases in order to see the effects of POAG on eye structure and function.
  • Exome sequencing of family-based samples to identify pseudo-Mendelian forms of POAG

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