Genetic variants associated with proliferative diabetic retinopathy in Latinos

Abstract

Purpose: Diabetic retinopathy (DR) is a leading cause of blindness in American working-age adults. It is a complication of diabetes mellitus characterized by the alteration of small blood vessels in the retina. There is a higher prevalence of DR in Latinos than in non-Hispanic Whites and African Americans. Here we describe a genome-wide association study (GWAS) of proliferative DR (PDR) in Latinos with type 2 diabetes mellitus (T2DM).

Methods: We conducted a population-based GWAS for DR using data recruited in the Los Angeles Latino Eye Study (LALES). The data were genotyped using the Illumina HumanOmniExpress Beadchip (~730K SNPs). All subjects were age 40 years and older. DR status was graded using the Early Treatment DR Study (ETDRS) scale. In order to reduce heterogeneity, we focused this analysis on severe diabetic retinopathy. We defined individuals with ETDRS grade ≥60 as cases (n = 95) and with grade 10-20 as controls (n = 552). We used logistic regression with adjustment for duration of diabetes, glycosylated hemoglobin level, systolic blood pressure and principal components of genetic ancestry. All statistical regression analyses were performed using PLINK.

Results: The top 3 SNPs associated with PDR are rs9300624 (P = 2.44E-6), rs2061803 (P = 7.32E-6) and rs7016616 (P = 9.58E-6). rs9300624 and rs7016616 are inside the NALCN-AS1 gene and the DLGAP2 gene, respectively, and rs2061803 is intergenic. NALCN-AS1 is associated with schizophrenia and bipolar disorder and DLGAP2 is expressed in the brain. It may be possible these brain-related genes are entangled with T2DM complications, such as PDR.

Conclusions: We discovered evidence for 3 novel loci for PDR in Latinos with T2DM. These loci may offer crucial insights in the molecular mechanism and provide candidate genes for further investigation of PDR in Latinos.

Keywords: 499 diabetic retinopathy • 539 genetics