Kathryn P Burdon, Rhys Fogarty, Nikolai Petrovsky,Mark Gillies, Mark Daniell, Sotoodeh Abhary,Gowthaman Govindarjan, Periasamy Sundaresan,Georgia Kaidonis, Alicia Jenkins, John Chang,Rohan Essex, Bishwanath Pal, Jamie E Craig

Purpose:
Diabetic Retinopathy (DR) is a potentiallyblinding diabetes complication with evidence forgenetic determinants. We aimed to conduct a wellpowered genome-wide association study (GWAS) toidentify susceptibility loci for DR.

Method:
2120 Caucasians with type 2 diabetes (T2D)were recruited from multiple hospitals and assessed forDR. A GWAS using the OmniExpress array (Illumina)was conducted in the first 1090 samples collected.Following data cleaning, association analysis was per-formed for any DR, sight-threatening DR (prolifera-tive, severe non-proliferative or significant macularedema), plus each DR subtype alone, compared toindividuals without DR. Top ranking polymorphisms(SNPs) were genotyped in the remainder of the cohort.Two replicated SNPs were typed in further replicationcohorts from Aravind Eye Hospital, India and an Aus-tralian type 1 diabetes (T1D) cohort.

Results:
SNP rs783992 near KCNB2 (voltage gatedpotassium channel, Kv2.2), was associated withany type of DR (p = 2.01 × 10 ? 8) and proliferativeDR (p = 7.5 × 10 ? 8) and also showed replication inthe second half of the initial cohort (p = 0.01), but notin the Indian or T1D cohorts. SNP rs9896052 nearGRB2 (Growth factor receptor-bound protein 2, anadaptor protein involved in signal transduction/cell communication) was associated with sight-threatening DR (p = 4.71 × 10 ? 8) and macular edema(p = 1.0 × 10 ? 6) and showed replication in the Cau-casian (p = 0.035), the Indian (p = 0.005) and the T1D(p = 0.022) cohorts.

Conclusion:
SNPs rs783992 and rs9896052 arereproducibly associated with DR in Caucasians withT2D and rs9896052 is also more broadly associated inother populations. This is the first GWAS for DR toprovide genome-wide significant association withreplication