African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.

Invest Ophthalmol Vis Sci
Authors
Keywords
Abstract

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.

Year of Publication
2015
Journal
Invest Ophthalmol Vis Sci
Volume
56
Issue
6
Pages
3999-4005
Date Published
2015 Jun
ISSN
1552-5783
URL
DOI
10.1167/iovs.15-16674
PubMed ID
26098467
PubMed Central ID
PMC4477259
Links
Grant list
Z99 EY999999 / Intramural NIH HHS / United States
K12 EY016335 / EY / NEI NIH HHS / United States
K12-EY16335 / EY / NEI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States