The Genetics of Glaucoma in Africa

Saakshi Bangera, DY Patil School of Biotechnology and Bioinformatics

Primary open-angle glaucoma (POAG) is the most generic subtype of irreversible blindness. Primary open-angle glaucoma primarily affects the people of African heritage. Among Europeans, the prevalence of POAG is approximately 1%, whereas, in African-Americans, this value ranges between 4-5%. Additionally, individuals of African ancestry experience an earlier onset as well as a more rapid progression of the illness. Despite the high frequency of the disease, the genetic mechanism of glaucoma in Africans is less known as compared to other populations. Due to a history of exploitation in the name of research as well as poor availability of research funding, there is a lack of understanding of Glaucoma. On top of that, there is a critical scarcity of specialized ophthalmologists and diagnostic equipment required. In addition, primary open-angle glaucoma is poorly understood by the population, which is why early symptoms are easily dismissed. These factors contribute to the huge gap in the understanding of African glaucoma.

The study in discussion addresses this evident gap in knowledge by understanding the genetic factors that make Africans more susceptible to glaucoma. 

The report consists of three parts:

• A genome-wide association scan (GWAS)
• Sequence analysis of early-onset Mendelian subtypes of glaucoma
• An educational drive to inform community members about genetic research and glaucoma

Result and Discussion

Many studies of Primary open-angle glaucoma and multi-ethnic meta-analysis demonstrate the genome-wide association of 127 loci. However, the relevancy of these loci to Africans and individuals of African descent is in doubt. The genome-wide association scan analysis of POAG demonstrates the differences in the genetic architecture of glaucoma in African people. The largest GWAS of primary open-angle glaucoma in Africans establishes a significant association with the APBB2 locus. This association is exclusive to individuals of African heritage. 

However, POAG is not the only disease that shows distinctness for a population of a certain heritage. For example, the mutation causing cystic fibrosis in people of Europe is less prevalent in Africans. In contrast, G1 and G2 alleles of the apolipoprotein L1 are associated with end-stage kidney disease (ESKD) in individuals of African heritage. Most people of African ancestry have these alleles, which explains the larger incidence of the disease. 

Differences in disease etiology have important consequences concerning both diagnosis and treatment of the disease. DNA genotyping is being greatly used to help with the diagnosis of such diseases. Two approaches are being used to do this:

• Detecting rare causative variants by gene sequencing
• Using polygenic risk scores to combine the effects of common genetic variants

Both of these approaches require huge databases of mutations that are population-specific. But such databases were constructed through analyzing Europeans and thus do not hold valid for African populations. Such problems will be solved if case-to-case studies are conducted. The genotypic data provides an understanding of the complex pathophysiology of glaucoma. This information reveals pathways and mechanisms of the progression of glaucoma. It also helps us to explicate novel therapeutic targets. 

Conclusion

Throughout the first 3 years of this study, more than 4000 samples of blood were collected for genotyping. Though the study was temporarily interrupted by the COVID-19 pandemic, it is continuing now. Genetic analysis of these samples helps us to understand the genetic design of primary open-angle glaucoma in Africa. A better understanding of the etiology of glaucoma will help to improve the diagnosis and treatment of the disease, eventually reducing the burden of human suffering. 

Also read: What causes post-concussion syndrome, now revealed!

Source: Olawoye, O., Chuka-Okosa, C., Akpa, O. et al. Eyes of Africa: The Genetics of Blindness: Study Design and Methodology. BMC Ophthalmol 21, 272 (2021). https://doi.org/10.1186/s12886-021-02029-8

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About the author: Saakshi is currently pursuing MSc in Biotechnology from DY Patil School of Biotechnology and Bioinformatics. She believes that she doesn’t have a specific area of interest yet. She wishes to explore toxicology and food biotechnology. She’s quite passionate about Biotechnology and aims to grab every opportunity she comes across.