Severe diabetic retinopathy is a leading cause of vision loss in type 1 diabetes and progresses over years, influenced by both environmental and genetic factors. A new study presented at EASD 2025, investigated genetic risk factors for severe diabetic retinopathy using both standard genome-wide association studies and survival analysis genome-wide association studies, leveraging time-to-event data.

The study included 2,737 individuals with severe diabetic retinopathy and 3,020 controls without the condition. Severe diabetic retinopathy events were defined by first laser treatment or proliferative diabetic retinopathy diagnosis. Samples were genotyped using Illumina HumanCoreExome arrays, with imputation based on a population-specific reference panel. Standard genome-wide association studies identified seven potential loci, with rs147155553 near the endothelin-3 gene approaching genome-wide significance. Survival analysis genome-wide association studies further revealed a genome-wide significant variant, rs534541023 in SNAP25 antisense RNA 1, whose significance persisted after adjusting for glycemic control.

Endothelin-3 is implicated in vascular endothelial dysfunction, while SNAP25 antisense RNA 1 regulates SNAP25 expression in retinal neurons, suggesting a time-dependent genetic influence on severe diabetic retinopathy development. These findings underscore the value of survival analysis in uncovering progressive disease mechanisms and potential therapeutic targets in diabetic retinopathy.