The Role of Genetic Ancestry as a Risk Factor for Primary Open-angle Glaucoma in African Americans.
Invest Ophthalmol Vis Sci
; 62(2): 28, 2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-33605984
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Negro ou Afro-Americano
/
Acuidade Visual
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Glaucoma de Ângulo Aberto
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Vigilância da População
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Polimorfismo de Nucleotídeo Único
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Pressão Intraocular
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Adult
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Female
/
Humans
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos