Dataset Information

Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure.

ABSTRACT: We determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness.Data were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the current substudy. A total of 31 ancestry informative markers (AIMs) with large allele frequencies differences between populations was used to calculate admixture proportion (implemented in STRUCTURE). Correlations with BGA adjusted for diagnosis, age, and sex for CCT and optic disc area using the whole group and RNFL thickness adjusted for age and sex for the normal study participants were determined.The mean percentage of African admixture was 79.6% in the self-described African Descent (AD) group and 3.5% in the European Descent (ED) group. Percent African ancestry was significantly correlated with CCT (? = -0.27, P < 0.0001) and disc area (? = 0.15, P < 0.0001), but only marginally associated with RNFL thickness (? = 0.20, P = 0.092) in adjusted models.The BGA correlates with variation in ocular features that significantly differ across racial groups and that have been associated with the development of glaucoma. While BGA can provide an objective measurement of the biologic component of self-described race for ocular research, for most nongenetic epidemiologic studies, self-described race may adequately describe the associations with these ocular characteristics. (ClinicalTrials.gov number, NCT00221923.).

SUBMITTER: Girkin CA

PROVIDER: S-EPMC4373542 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure.

Girkin Christopher A CA Nievergelt Caroline M CM Kuo Jane Z JZ Maihofer Adam X AX Huisingh Carrie C Liebmann Jeffrey M JM Ayyagari Radha R Weinreb Robert N RN Ritch Robert R Zangwill Linda M LM

Investigative ophthalmology & visual science 20150305 3

<h4>Purpose</h4>We determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness.<h4>Methods</h4>Data were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the curr ...[more]

PMID: 25744975

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Project description:PURPOSE:To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (?PPA) between individuals of African descent (AD) and European descent (ED). DESIGN:Prospective, multicenter, observational cohort. PARTICIPANTS:A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS:Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and ?PPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with ?PPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. MAIN OUTCOME MEASURES:Differences in frequency of DH and prevalence of ?PPA. RESULTS:A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P < 0.001), whereas ?PPA had higher prevalence in AD eyes (675 eyes [72%] vs. 659 eyes [64%]; P < 0.001). In the final multivariable model, after controlling for confounders, AD eyes were less likely to have at least 1 detected DH than ED eyes (odds ratio [OR], 0.21; 95% CI, 0.10-0.45; P < 0.001) but were more likely to have ?PPA than ED eyes (OR, 1.55; 95% CI, 1.12-2.14; P = 0.008). CONCLUSIONS:Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of ?PPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of ?PPA affect the likelihood of glaucomatous progression.

Project description:PURPOSE:To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN:Cross-sectional, case-control study. PARTICIPANTS:Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS:Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES:Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS:The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS:With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

Project description:PurposeTo find genetic contributions to glaucoma in African Americans.DesignCross-sectional, case-control study.ParticipantsOne thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine.MethodsMegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs).Main outcome measuresPrimary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946).ResultsEighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively.ConclusionsA novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

Dataset Information

Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure.

Publications

Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure.

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