Editors Selection IGR 21-4

Risk Factors: African Genetic Ancestry as a Risk Factor for Glaucoma

Chiea Chuen Khor

Comment by Chiea Chuen Khor on:

91769 Time Lag Between Functional Change and Loss of Retinal Nerve Fiber Layer in Glaucoma, Gardiner SK; Mansberger SL; Fortune B, Investigative Ophthalmology and Visual Science, 2020; 61: 5

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The authors assessed the contribution of African ancestry and potential risk of primary open-angle glaucoma (POAG) using a two-stage study design. This study comprised discovery (1783 participants with POAG and 2047 unaffected control participants) and replication stages (755 participants with POAG and 1380 unaffected control participants), both of which recruited participants who self-reported African American ancestry from Pennsylvania, USA. Consistently in both stages, the authors reported that participants with POAG had a significantly higher component of African ancestry (as determined using genetically derived ancestry scores from genome-wide genotyping of representative genetic markers) compared to participants without POAG (Odds Ratio of between 1.14 to 1.27 for every standard deviation increase in ancestry scores).

The authors also performed secondary analysis by constructing a polygenic risk score based on 23 genetic variants previously reported to be associated with POAG risk in (mostly) European ancestry studies. They assessed the utility and performance of this polygenic risk score in their study on African American ancestry participants and observed that each point increase in polygenic risk score was associated with an Odds Ratio of 1.08 increased risk of POAG in African American ancestry participants.

Although there are shared genetic loci between African ancestry participants and European ancestry participants significant differences in terms of genetic architecture could exist

I found this large, well-powered and well-controlled study to be very timely, as the genetic architecture of POAG in persons of African ancestry remain understudied, despite the population-wide disease prevalence being significantly higher in African ancestry participants compared to European- or Asian ancestry participants.1,2 Emerging studies in this area have suggested that although there are shared genetic loci between African ancestry participants and European ancestry participants,3 significant differences in terms of genetic architecture could exist.4-6 Most notably, the Odds Ratio per-unit increase in terms of polygenic risk score was modest (OR = 1.08) compared to well known risk factors of POAG such as age (OR between 1.70 to 2.18 for every ten years increase in age) and sex (OR between 1.35 to 2.61 for male sex). This could be due to the risk score being based on European ancestry studies.

In conclusion, there is an increasing need to evaluate the genetic architecture of glaucoma and other blinding disorders in understudied and underserved populations, such as in participants of African ancestry. Such studies often yield unexpected and extremely helpful insights that illuminate disease biology and open up new approaches to therapy.7


  1. Budenz DL, et al. JAMA Ophthalmol 2013; 131:651-658.
  2. Choquet H, et al. Nat Commun. 2018; 9(1):2278.
  3. Gharahkhani P, et al. Nat Commun. 2021; 12(1):1258.
  4. Hauser MA, et al. JAMA. 2019; 322(17):1682-1691.
  5. Bonnemaijer PW, et al. Hum Genet. 2018;137(10):847-862.
  6. Taylor KD et al., Ophthalmology. 2019;126(1): 38-48.
  7. Cohen JC, et al. N Engl J Med. 2006; 354:1264-1272.

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