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Abstract #91679 Published in IGR 21-4
The Role of Genetic Ancestry as a Risk Factor for Primary Open-angle Glaucoma in African Americans
Cole BS; Gudiseva HV; Pistilli M; Salowe R; McHugh CP; Zody MC; Chavali VRM; Ying GS; Moore JH; O'Brien JMInvestigative Ophthalmology and Visual Science 2021; 62: 28
PURPOSE: POAG is the leading cause of irreversible blindness in African Americans. In this study, we quantitatively assess the association of autosomal ancestry with POAG risk in a large cohort of self-identified African Americans. METHODS: Subjects recruited to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study were classified as glaucoma cases or controls by fellowship-trained glaucoma specialists. POAAGG subjects were genotyped using the MEGA Ex array (discovery cohort, n = 3830; replication cohort, n = 2135). Population structure was interrogated using principal component analysis in the context of the 1000 Genomes Project superpopulations. RESULTS: The majority of POAAGG samples lie on an axis between African and European superpopulations, with great variation in admixture. Cases had a significantly lower mean value of the ancestral component q0 than controls for both cohorts (P = 6.14-4; P = 3-6), consistent with higher degree of African ancestry. Among POAG cases, higher African ancestry was also associated with thinner central corneal thickness (P = 2-4). Admixture mapping showed that local genetic ancestry was not a significant risk factor for POAG. A polygenic risk score, comprised of 23 glaucoma-associated single nucleotide polymorphisms from the NHGRI-EBI genome-wide association study catalog, was significant in both cohorts (P < 0.001), suggesting that both known POAG single nucleotide polymorphisms and an omnigenic ancestry effect influence POAG risk. CONCLUSIONS: In sum, the POAAGG study population is very admixed, with a higher degree of African ancestry associated with an increased POAG risk. Further analyses should consider social and environmental factors as possible confounding factors for disease predisposition.
Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Full articleClassification:
9.2.2 Other risk factors for glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)
1.2 Population genetics (Part of: 1 General aspects)
