부산대학교 도서관

Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries. Trial Registration:NCT00473330, NCT00473382, NCT03622580, NCT03622593, NCT04108156. Author summary: Although twin and family studies have clearly shown that genes play a role in the development of diabetic macular edema (DME), confirmed risk loci have remained elusive. Here, in the largest genetic study of DME to date with >7,000 individuals, we utilize data from clinical trials and large biobanks to identify and confirm two risk loci associated with risk of DME, one on Chromosome 19 and another on Chromosome 22. The locus on Chromosome 19 contains two genes of interest, PLVAP and ANKLE1. The locus on Chromosome 22 is tagged by a functional variant in the gene APOL1, a gene previously associated with kidney disease in African descent populations, suggesting APOL1 plays a broader role in diabetic complications than previously thought. Further studies of the genes at these loci will shed light on how they affect DME. These findings are important because they represent a significant step forward in the understanding of the genetic component to diabetic eye disease. [ABSTRACT FROM AUTHOR]