Genetics of Diabetic Retinopathy

Diabetic retinopathy (DR) is a polygenic disorder. Twin studies and familial aggregation studies have documented clear familial clustering. Heritability has been estimated to be as high as 27 % for any DR and 52 % for proliferative diabetic retinopathy (PDR), an advanced form of the disease. Linkage analyses, candidate gene association studies and genome-wide association studies (GWAS) performed to date have not identified any widely reproducible risk loci for DR. Combined analysis of the data from multiple GWAS is emerging as an important next step to explain the unaccounted heritability. Key factors to future discovery of the genetic underpinnings of DR are precise DR ascertainment, a focus on the more heritable disease forms such as PDR, stringent selection of control participants with regards to duration of diabetes, and methods that allow combination of existing datasets from different ethnicities to achieve sufficient sample sizes to detect variants with modest effect sizes.