Open AccessThe Role of Genetic Ancestry as a Risk Factor for Primary Open-angle Glaucoma in African Americans
Author(s) -
Brian Cole,
Harini V. Gudiseva,
Maxwell Pistilli,
Rebecca Salowe,
Caitlin McHugh,
Michael C. Zody,
Venkata R M Chavali,
Gui Shuang Ying,
Jason H. Moore,
Joan M. O’Brien
Publication year - 2021
Publication title -
investigative ophthalmology and visual science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.935
H-Index - 218
eISSN - 1552-5783
pISSN - 0146-0404
DOI - 10.1167/iovs.62.2.28
Subject(s) - glaucoma , single nucleotide polymorphism , cohort , open angle glaucoma , context (archaeology) , population , medicine , risk factor , confounding , demography , ophthalmology , cohort study , genetic genealogy , genome wide association study , genetics , genotype , biology , environmental health , gene , paleontology , sociology
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.