Primary Open-Angle African American Glaucoma Genetics Research Articles

Socioeconomic and environmental factors associated with glaucoma in an African Ancestry Population: findings from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study.

Glaucoma is the leading cause of irreversible blindness, disproportionately affecting individuals of African ancestry. Limited research has examined the impact of neighbourhood quality and socioeconomic factors on primary open-angle glaucoma (POAG) risk in this population. This study aims to address these gaps by evaluating associations between ocular health and neighbourhood characteristics using geospatial data. We conducted a case-control study with 5192 African ancestry individuals from the Philadelphia area using data from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Geocoded U.S. Census data were merged with individual-level demographics and neighbourhood-level measures, including air quality, food accessibility, and socioeconomic indicators, to assess their association with glaucoma risk and severity. The study included 3039 controls (58.5%) and 2153 POAG cases (41.5%). Higher POAG risk was associated with older age (OR 1.72 per 10-year increase, p < 0.001), male gender (OR 2.04, p < 0.001), lower BMI (OR 0.87 per 10 kg/m2 increase, p = 0.003), and nonuse of alcohol (OR 0.56 for alcohol use, p < 0.001). Low food access was more common in controls (OR 0.86, p = 0.03), and severe POAG cases were associated with lower homeownership rates (OR 0.95 per 10% increase, p = 0.049). However, most socioeconomic and environmental factors (air quality, education, income, occupation, family structure) were not significantly linked to POAG risk or severity. Socioeconomic status did not significantly protect against POAG in African ancestry individuals. Individual factors were more influential, suggesting neighbourhood and socioeconomic factors may have a lesser impact than previously hypothesised.

Primary Open-Angle Glaucoma Is Associated with Short-Term Memory Decline and Dementia in Individuals of African Ancestry.

Background: Over the last decade, studies have suggested that primary open-angle glaucoma (POAG) may be associated with cognitive impairment and dementia, as both pathologies are age-related neurodegenerative processes. It remains unclear to what extent neurodegeneration in POAG extends to other neurological functions beyond vision, such as cognition. This follow-up study examined the potential association between POAG and cognitive decline in an African ancestry population. Methods: The Telephone-Montreal Cognitive Assessment (T-MoCA) was administered to POAG cases and controls previously enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Cases were assessed for retinal nerve fiber layer (RNFL) thickness and for the presence of dementia via chart review. Comparisons between POAG cases and controls were performed using two-sample t-tests for the T-MoCA total score and five subsection scores, and using chi-squared tests for incidence of dementia. Current scores were compared to scores from this same cohort from 7 years prior. Results: The T-MoCA was administered to 13 cases and 20 controls. The mean ± standard deviation (SD) T-MoCA total score was 15.5 ± 4.0 in cases and 16.7 ± 3.5 in controls (p = 0.36). However, there was a borderline significant difference in the delayed recall sub-score (2.3 ± 1.6 for cases vs. 3.4 ± 1.5 for controls, p = 0.052) and a significant difference in its sub-domain, the memory index score (MIS, 9.1 ± 4.3 for cases vs. 12.1 ± 3.0 for controls, p = 0.02). There were no significant differences between cases and controls for the remaining subsections. During 7 years of follow-up, a higher incidence of dementia was noted in POAG cases (7.1% for cases vs. 0% for controls, p = 0.058). Over 7 years, there was no significant deterioration in the cognitive performance of cases versus controls, and no association was seen between RNFL thinning and cognitive impairment. Conclusions: In this small-sample follow-up study of African ancestry individuals, POAG cases demonstrated worse short-term memory and higher incidence of dementia compared to controls. Future larger studies are needed to further investigate the presence and impact of neurodegeneration in POAG.

Optic cup morphology associated with glaucomatous damage: Findings from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study

PurposeWhile it has been well established that advanced glaucoma is associated with a large cup-to-disc ratio (CDR), it is not known if the shape of the cup, particularly excavated cups with expanded lower portions (bean-pot cups), play any additional role in glaucomatous damage. We investigated this among individuals of African ancestry, a population that is more vulnerable to glaucoma than any other ethnic group. DesignCase-control study Methods SettingInstitutional (University of Pennsylvania) Subjects3,255 eyes from 1,734 glaucoma cases from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. ProcedureTwo graders independently assessed quantitative and qualitative aspects of the optic cup, with any discrepancies adjudicated by an ophthalmologist. The predominant cup shape (>50 %) was chosen in cases in which features of two or more cup shapes were present in the same eye. Comparisons of demographic and ocular characteristics among three cup shape groups (conical, cylindrical, and bean-pot) performed using generalized linear models, and generalized estimated equations applied to account for inter-eye correlation. Main Outcome MeasuresQualitative features of cup shape and phenotypic traits, in conjunction with demographic and genetic information. ResultsOf 3,255 eyes, a total of 1,339 (41.1 %) exhibit a conical cup shape, 1,470 (45.2 %) have a cylindrical cup shape, and 446 (13.7 %) display a bean-pot cup shape. Compared to other cup morphology, bean-pot cups are significantly associated with lower MD, larger CDR, higher IOP, thinner RNFL, and worse VA in logMAR (all p < 0.001). Genetic analysis does not show any association between various genetic variants and cup shape. Factors independently predictive of bean-pot cupping include younger age at diagnosis (aOR 0.96 per 1 year increase in age of enrollment, p < 0.0001), CDR (adjusted odds ratio (aOR) 1.87, p < 0.0001), and the presence of certain optic disc features, including visible pores in the LC (aOR 2.76, p < 0.0001), nasalization of vessels (aOR 2.64, p < 0.0001), and vessel bayonetting (aOR 2.94, p < 0.0001). ConclusionThis study shows the clinical significance of different cup shapes in glaucoma in an African ancestry population and suggests that bean-pot cups are associated with the most severe glaucomatous damage, independent of cup-disc ratio. This association should be considered when determining prognosis following glaucoma interventions.

Factors Associated with Large Cup-to-Disc Ratio and Blindness in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study.

Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry. In these patients' eyes, a large cup-to-disc ratio (LCDR > 0.90) suggests greater retinal ganglion cell loss, though these patients often display varied visual ability. This study investigated the prevalence and risk factors associated with LCDR in African ancestry individuals with POAG and explored the differences between blind (>20/200) and not blind (≤20/200) LCDR eyes. A case-control methodology was used to investigate the demographic, optic disc, and genetic risk factors of subjects in the Primary Open-Angle African American Glaucoma Genetics Study. Risk factors were analyzed using univariable and multivariable logistic regression models with inter-eye correlation adjusted using generalized estimating equations. Out of 5605 eyes with POAG, 1440 eyes (25.7%) had LCDR. In the multivariable analysis, LCDR was associated with previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.04), decreased mean deviation (OR = 1.08), increased pattern standard deviation (OR = 1.06), thinner retinal nerve fiber layer (OR = 1.05), nasalization of vessels (OR = 2.67), bayonetting of vessels (OR = 1.98), visible pores in the lamina cribrosa (OR = 1.68), and a bean-shaped cup (OR = 2.11). Of LCDR eyes, 30.1% were classified as blind (≤20/200). In the multivariable analysis, the statistically significant risk factors of blindness in LCDR eyes were previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.05), decreased mean deviation (OR = 1.04), and decreased pattern standard deviation (OR = 0.90). These findings underscore the importance of close monitoring of intraocular pressure and visual function in African ancestry POAG patients, particularly those with LCDR, to preserve visual function.

Prevalence and Factors Associated with Optic Disc Tilt in the Primary Open-Angle African American Glaucoma Genetics Study

To investigate the prevalence and factors associated with optic disc tilt in the eyes of Black Americans with glaucoma. Cross-sectional. Subjects with glaucoma participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Stereo pairs of optic disc images were assessed independently by POAAGG-certified nonphysician graders for quantitative features including maximum and minimum linear disc diameters, and qualitative features including gradeability of images, shape of the cup, rim plane position, β-peripapillary atrophy, sloping region adjacent to the outer disc margin, and rim pallor. Discrepancies were adjudicated by an ophthalmologist. Descriptive statistics and P values were generated for associations of tilt with demographic and ocular characteristics. Stepwise multivariable analysis was performed with logistic regression using Generalized Estimating Equations (GEEs) to account for inter-eye correlation within subjects. Tilt Ovality Index (TOI) of >1.30 and Stereoscopically Identified optic disc Tilt (SIT). Among 1251 subjects with data on both eyes, 104 (8.3%) had TOI. Subjects with TOI were less likely to be male (adjusted odds ratio [aOR], 0.46, 95% confidence interval [CI], 0.29-0.74, P < 0.001). Eyes with TOI were less likely to have large cup disc ratios (aOR, 0.18, 95% CI, 0.06-0.53, P < 0.001) and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.31, 95% CI, 0.19-0.49, P < 0.001). Among 1007 subjects with data on both eyes, 254 (25.2%) had SIT. Subjects with SIT were younger (aOR, 0.95, 95% CI, 0.93-0.96, P < 0.001), and eyes with SIT were more likely to have oval-shaped discs compared with round discs (aOR, 1.82, 95% CI, 1.32-2.52, P < 0.001), more likely to have a sloping region adjacent to the outer disc margin instead of being flat (aOR, 3.26, 95% CI, 2.32-4.59, P < 0.001), and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.59, 95% CI, 0.41-0.85, P < 0.001). Both TOI and SIT were not associated with myopia. There are substantial numbers of tilted optic discs in glaucoma patients with African ancestry. They occur more frequently in female subjects and younger subjects and are associated with several ocular features but not with myopia.

Association of the SNP rs112369934 near TRIM66 Gene with POAG Endophenotypes in African Americans

We investigated the association of the single nucleotide polymorphism (SNP) rs112369934 near the TRIM66 gene with qualitative and quantitative phenotypes of primary open-angle glaucoma (POAG) in African Americans (AA). AA subjects over 35 years old were recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study in Philadelphia, PA. Glaucoma cases were evaluated for phenotypes associated with POAG pathogenesis, and the associations between rs112369934 and phenotypes were investigated by logistic regression analysis and in gender-stratified case cohorts: The SNP rs112369934 was found to have a suggestive association with retinal nerve fiber layer (RNFL) thickness and cup-to-disc ratio (CDR) in 1087 male AA POAG cases, individuals with the TC genotype having thinner RNFL (95% CI 0.85 to 6.61, p = 0.01) and larger CDR (95% CI −0.07 to −0.01, p = 0.02) than those with wildtype TT. No other significant associations were found. In conclusion SNP rs112369934 may play a role in POAG pathogenesis in male AA individuals. However, this SNP has been implicated in higher POAG risk in both male and female AA POAG cases.

Evaluation of the Cirrus High-Definition OCT Normative Database Probability Codes in a Black American Population

Race-adjusted interpretation of data from Cirrus high-definition OCT (HD-OCT) devices is not standard practice. The aim of this study is to evaluate differences in peripapillary retinal nerve fiber layer (RNFL) thickness between healthy Black Americans and the Cirrus HD-OCT normative database. This is a cross-sectional observational study using control patients recruited from the greater Philadelphia, Pennsylvania, area. A total of 466 eyes were included in this study. Subjects were retrospectively identified from the control cohort of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Using an age-stratified or linear regression method, we reclassified white-green-yellow-red color probability codes for RNFL thicknesses by quadrant. The distribution of reclassified color codes was compared with the expected 5%-90%-4%-1% percentiles and to the original color codes by the Cirrus machine. Average RNFL thickness in the POAAGG control cohort was thinner than in the Cirrus normative database in all except the nasal quadrant. The original color codes of the POAAGG cohort did not fall into the expected distributions, with more RNFL measurements assigned as white and red codes than expected (9.5% and 1.7%) and fewer measurements assigned as green and yellow codes than expected (85.3% and 3.5%) (P < 0.001). Compared with the original Cirrus machine, reclassification using linear regression produced color codes closest to the expected distributions (P= 0.09). The proportion of abnormal results shifted closer to the expected 5% in the nasal (1.3%, P < 0.001 vs. 3.0%, P= 0.048) and temporal (8.2%, P= 0.002 vs. 3.6%, P= 0.18) quadrants. Results further establish the presence of structural differences in the RNFL of Black American patients. Color code reclassification suggests that the existing Cirrus database may not be accurately evaluating glaucomatous nerves in patients of African descent. This study addresses an unmet need to assess Cirrus HD-OCT color probability codes in a Black American population.

The Role of Genetic Ancestry as a Risk Factor for Primary Open-angle Glaucoma in African Americans.

PurposePOAG 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.MethodsSubjects 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.ResultsThe 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.ConclusionsIn 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.

Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study: gender and risk of POAG in African Americans.

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects’ mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44–1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences.

SNP located in an AluJb repeat downstream of TMCO1, rs4657473, is protective for POAG in African Americans

AimsTo determine the association of single nucleotide polymorphisms (SNPs) downstream from the TMCO1 gene with primary open-angle glaucoma (POAG) in African Americans (AA).MethodsAA subjects were recruited for the Primary Open-Angle...

The association of mitochondrial DNA haplogroups with POAG in African Americans

Mitochondrial dysfunction has been implicated in the pathogenesis of primary open-angle glaucoma (POAG). However, the potential significance of mitochondrial DNA (mtDNA) haplogroups to POAG has not been evaluated in the overaffected African American population. To investigate the association of mtDNA haplogroups with POAG and its phenotypic characteristics, genotyping data from 4081 African American subjects (1919 cases and 2162 controls) was analyzed using 1293 positions on mtDNA. The overall frequency of mtDNA haplogroups in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort was 37% L3, 29% L2, 21% L1, 4% L0, and 10% non-African haplogroups (non-L). When all haplogroups (L0, L1, L2, and non-L) were compared against theL3 reference group, after adjusting by age and principal component of ancestry, the non-L3 haplogroups showed higher risk of POAG (OR-1.19, p = 0.02), with a particularly strong association among males (OR = 1.41, p = 0.003). More specifically the non-L group was associated with higher POAG risk than the L3 haplogroup (OR = 1.77, p = 0.007, Bonferroni adjusted p = 0.027) and to the L3e (n = 256, OR = 1.92, p = 0.007, Bonferroni adjusted p = 0.029). No significant association was found when genders were analyzed together or in female only analysis. There were no significant differences in various POAG endophenotypes across mtDNA haplogroups. This study expands our knowledge of mitochondrial genetics and mtDNA haplogroup associations in African American POAG. Further work is needed to better understand the functional role of mtDNA polymorphisms and their interactions with nuclear genes that affect POAG.

Non-physician grader reliability in measuring morphological features of the optic nerve head in stereo digital images.

To introduce a new method of grading optic nerve stereo disc photographs and evaluate reproducibility of assessments by non-physician graders in a reading center. Three non-physician graders, experienced in grading features of the retina but not the optic nerve head (ONH), were trained by glaucoma specialists to assess digital stereo color images of the ONH. These graders assessed a total of 2554 digital stereo disc images from glaucoma cases and controls participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study by outlining the optic cup and disc. Inter-grader reproducibility of area, height, and width measurements was analyzed. Among all images, the intraclass correlation (95% confidence interval) was 0.90 (0.89, 0.90) for the cup area using only color cues; 0.92 (0.91, 0.92) for the cup area using contour and vascular cues; and 0.99 (0.99, 0.99) for the optic disc area. The intraclass correlation for cup-to-disc ratio (CDR) was 0.61 (0.58, 0.63), as determined by the ratio of optic cup area to optic disc area (using contour and vascular cues). The CDR difference by graders for area was ≤ 0.1 in 65% of images using color/vascular cues and ≤0.1 in 71% of images using color cues. After adequate training, non-physician graders were able to measure the optic nerve CDR with high inter-grader reliability.

Family History in the Primary Open-Angle African American Glaucoma Genetics Study Cohort

To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort. FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities. Positive FH was associated with increased risk of POAG (age-adjusted odds ratio and 95% confidence interval 3.4 [2.8, 4.1]). In age-adjusted analysis among POAG cases, positive FH was associated with younger age (P < .001), female sex (P < .001), hypertension (P= .006), use of hypertension medication (P=.03), and prior glaucoma surgery (P= .02). Cases with positive FH also had thicker retinal nerve fiber layers (P= .03). The risk conferred by positive FH suggests strong genetic underpinnings for some patients with this disease, which will be investigated by genome-wide association studies and whole exome sequencing. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Cost and yield considerations when expanding recruitment for genetic studies: the primary open-angle African American glaucoma genetics study

BackgroundAfrican Americans have been historically under-represented in genetic studies. More research is needed on effective recruitment strategies for this population, especially on approaches that supplement traditional clinic enrollment. This study evaluates the cost and efficacy of four supplemental recruitment methods employed by the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study.MethodsAfter enrolling 2304 patients from University of Pennsylvania ophthalmology clinics, the POAAGG study implemented four new recruitment methods to supplement clinic enrollment. These methods included: 1) outreach in the local community, 2) in-house screening of community members (“in-reach”), 3) expansion to two external sites, and 4) sampling of the Penn Medicine Biobank. The cost per subject was calculated for each method and enrollment among cases, controls, and suspects was reported.ResultsThe biobank offered the lowest cost ($5/subject) and highest enrollment yield (n = 2073) of the four methods, but provided very few glaucoma cases (n = 31). External sites provided 88% of cases recruited from the four methods (n = 388; $85/subject), but case enrollment at these sites declined over the next 9 months as the pool of eligible subjects was depleted. Outreach and in-reach screenings of community members were very high cost for low return on enrollment ($569/subject for 102 subjects and $606/subject for 45 subjects, respectively).ConclusionsThe biobank offered the most cost-effective method for control enrollment, while expansion to external sites was necessary to recruit richly phenotyped cases. These recruitment methods helped the POAAGG study to exceed enrollment of the discovery cohort (n = 5500) 6 months in advance of the predicated deadline and could be adopted by other large genetic studies seeking to supplement clinic enrollment.

Factors associated with participation by African Americans in a study of the genetics of glaucoma

ABSTRACTObjective: African Americans have been historically underrepresented in research studies. Our aim was to evaluate factors influencing enrollment in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study.Design: Patients approached to enroll in the POAAGG study were asked to complete a 15-item survey addressing demographic characteristics, knowledge of genetics and glaucoma, and opinions on human research. Survey responses were compared between subjects who enrolled (Enrollers) and did not enroll (Decliners) in the POAAGG study.Results: Enrollers (N = 190) were 3.7 years younger (P = 0.007) and had similar gender, education, and income level to Decliners (N = 117). Knowledge about genetics and glaucoma was similar between groups. Enrollers were more comfortable providing DNA for research studies (93.1% vs 54.1%; P < 0.001) and more likely to have participated in prior studies (P = 0.003) and consider participating in future studies (P < 0.001). Among Decliners, lack of time was the primary reason given for not enrolling.Conclusion: To increase participation of African Americans in genetic research studies, efforts should be made to raise comfort with DNA donation.

Risk Factors Associated with Progression to Blindness from Primary Open-Angle Glaucoma in an African-American Population

ABSTRACTPurpose: To determine the risk factors associated with progression to blindness from primary open-angle glaucoma (POAG) in an African-American population.Methods: This study examined 2119 patients enrolled in the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study. A total of 59 eyes were identified as legally blind as a result of POAG (cases) and were age-and sex-matched to 59 non-blind eyes with glaucoma (controls). Chart reviews were performed to record known and suspected risk factors.Results: Cases were diagnosed with POAG at an earlier age than controls (p = 0.005). Of the 59 eyes of cases, 16 eyes (27.1%) presented with blindness at diagnosis. Cases had worse visual acuity (VA) at diagnosis (p < 0.0001), with VA worse than 20/40 conferring a 27 times higher risk of progression to blindness (p = 0.0005). Blind eyes also demonstrated more visual field defects (p = 0.01), higher pre-treatment intraocular pressure (IOP; p < 0.0001), and higher cup-to-disc ratio (p = 0.006) at diagnosis. IOP was less controlled in cases, and those with IOP ≥21 mmHg at more than 20% of follow-up visits were 73 times more likely to become blind (p < 0.0001). Cases missed a greater number of appointments per year (p = 0.003) and had non-adherence issues noted in their charts more often than controls (p = 0.03). However, other compliance data did not significantly differ between groups.Conclusion: Access to care, initial VA worse than 20/40, and poor control of IOP were the major risk factors associated with blindness from POAG. Future studies should examine earlier, more effective approaches to glaucoma screening as well as the role of genetics in these significantly younger patients who progress to blindness.

Saliva DNA quality and genotyping efficiency in a predominantly elderly population.

BackgroundThe question of whether DNA obtained from saliva is an acceptable alternative to DNA from blood is a topic of considerable interest for large genetics studies. We compared the yields, quality and performance of DNAs from saliva and blood from a mostly elderly study population.MethodsTwo thousand nine hundred ten DNAs from primarily elderly subjects (mean age ± standard deviation (SD): 65 ± 12 years), collected for the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study, were evaluated by fluorometry and/or spectroscopy. These included 566 DNAs from blood and 2344 from saliva. Subsets of these were evaluated by Sanger sequencing (n = 1555), and by microarray SNP genotyping (n = 94) on an Illumina OmniExpress bead chip platform.ResultsThe mean age of subjects was 65, and 68 % were female in both the blood and saliva groups. The mean ± SD of DNA yield per ml of requested specimen was significantly higher for saliva (17.6 ± 17.8 μg/ml) than blood (13.2 ± 8.5 μg/ml), but the mean ± SD of total DNA yield obtained per saliva specimen (35 ± 36 μg from 2 ml maximum specimen volume) was approximately three-fold lower than from blood (106 ± 68 μg from 8 ml maximum specimen volume). The average genotyping call rates were >99 % for 43 of 44 saliva DNAs and >99 % for 50 of 50 for blood DNAs. For 22 of 23 paired blood and saliva samples from the same individuals, the average genotyping concordance rate was 99.996 %. High quality PCR Sanger sequencing was obtained from ≥ 98 % of blood (n = 297) and saliva (n = 1258) DNAs. DNA concentrations ≥10 ng/μl, corresponding to total yields ≥ 2 μg, were obtained for 94 % of the saliva specimens (n = 2344).ConclusionsIn spite of inferior purity, the performance of saliva DNAs for microarray genotyping was excellent. Our results agree with other studies concluding that saliva collection is a viable alternative to blood. The potential to boost study enrollments and reduce subject discomfort is not necessarily offset by a reduction in genotyping efficiency. Saliva DNAs performed comparably to blood DNAs for PCR Sanger sequencing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0172-y) contains supplementary material, which is available to authorized users.

The Primary Open-Angle African American Glaucoma Genetics Study: Baseline Demographics

To describe the baseline characteristics of the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study cohort, the largest African American population with primary open-angle glaucoma (POAG) recruited at a single institution (University of Pennsylvania [UPenn], Department of Ophthalmology, Scheie Eye Institute) to date. Population-based, cross-sectional, case-control study. A total of 2520 African American subjects aged 35 years or more who were recruited from the greater Philadelphia, Pennsylvania area. Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current ZIP codes surrounding UPenn were recorded and US census data were queried to infer socioeconomic status. The eye examination included measurement of visual acuity (VA) and intraocular pressure, and a detailed anterior and posterior segment examination, including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography, and measurement of central corneal thickness. The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco use, ocular conditions (including blindness, cataract, nonproliferative diabetic retinopathy, and age-related macular degeneration), and use of ocular medication and surgery were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort. Of the 2520 African Americans recruited to the POAAGG study to date, 2067 (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria and completed the detailed clinical ocular examination. Cases were more likely to have a lower BMI (P < 0.01) and report a history of blindness (VA of ≤20/200; P < 0.001), whereas controls were more likely to have diabetes (P < 0.001), have nonproliferative diabetic retinopathy (P = 0.02), and be female (P < 0.001). Study participants were drawn largely from predominantly African American neighborhoods of low income, high unemployment, and lower education surrounding UPenn. The POAAGG study has currently recruited more than 2000 African Americans eligible for a POAG genetics study. Blindness and low BMI were significantly associated with POAG. This population was predominantly recruited from neighborhoods whose population income exists at or near the federal poverty level.