Author(s): Tandon A, Chen CJ, Penman A, Hancock H, James M, Husain D, Andreoli C, Li X, Kuo JZ, Idowu O, Riche D, Papavasilieou E, Brauner S, Smith SO, Hoadley S, Richardson C, Kieser T, Vazquez V, Chi C, Fernandez M, Harden M, Cotch MF, Siscovick D, Taylor HA, Wilson JG, Reich D, Wong TY, Klein R,Klein BE, Rotter JI, Patterson N, Sobrin L. African ancestry analysis and admixture genetic mapping for proliferative diabetic retinopathy in African Americans. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3999-4005. doi: 10.1167/iovs.15-16674. PMID 26098467
PURPOSE To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D).
METHODS Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software.
RESULTS In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1.
CONCLUSIONS In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.