Native American ancestry is associated with severe diabetic retinopathy in Latinos

Abstract

Purpose: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Studies have observed that Latinos have a higher prevalence of DR than whites. The purpose of this study is to test the association between genetic admixture and severe DR in Latinos with type 2 diabetes mellitus (T2DM).

Methods: We conducted a case-control study using 944 T2DM subjects from the Los Angeles Latino Eye Study. Cases (n = 135) were defined as proliferative or severe nonproliferative DR subjects. Controls (n = 809) were other diabetic subjects in the cohort. Genotyping was performed on the Illumina OmniExpress BeadChip. We estimated genetic ancestry in Latinos using STRUCTURE with the HapMap reference panels. Univariate and multivariate logistic regression analyses were used to test the relationship between the proportions of genetic ancestry and severe DR.

Results: Native American ancestry (NAA) in Latino T2DM subjects is associated significantly with severe DR (P = 0.002). The association remained significant (P = 0.005) after adjusting for age, sex, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, education, and income. We also validated the NAA estimates in Latinos using ADMIXTURE with the 1000 Genomes Project reference panels and obtained consistent results.

Conclusions: Our results demonstrate for the first time to our knowledge that NAA is a significant risk factor for severe DR in Latinos.

Keywords: Latinos; Native American; diabetic retinopathy; genetic ancestry.

Figure 1

Individual genetic ancestry estimates. Each individual is represented by a vertical bar, which is composed of three colored segments corresponding to the proportions of genetic ancestry from three ancestry populations. Native American, African, and European ancestries are colored dark yellow, blue, and purple, respectively. The x-axis and y-axis denote subjects and proportions of genetic ancestry, respectively. Subjects are sorted by their NAA to aid visualization. Ticks on the x-axis are severe DR subjects.

Figure 2

Pairwise plots of the NAA estimates from STRUCTURE and ADMIXTURE. The x-axis and y-axis denote STRUCTURE NAA and ADMIXTURE NAA estimates, respectively. If the two estimates for the same subjects match with each other perfectly, they would fall on the diagonal line. We see that the STRUCTURE and ADMIXTURE NAA estimates agree with each very well with a correlation coefficient greater than 0.99.