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Multiple genome-wide association studies of type 2 diabetes implicate several genes are associated with diabetic retinopathy based on UK Biobank

Cai, T.; Pan, Q.; Tao, Y.; Nangia, C.; Rajendrakumar, A. L.; Dottorini, T.; Haque, M.; Palmer, C.; Meng, W.

2023-12-03 ophthalmology
10.1101/2023.12.02.23299320 medRxiv
Show abstract

PurposeTo identify the genetic variants associated with diabetic retinopathy in type 2 patients from the UK Biobank cohort (n = 17,015) and supporting replication cohorts GODARTS (n = 5,013), GOSHARE (n = 1,754), Caucasian Australians (n = 518), FinnGen (n = 206,664) and Chinese (n = 1,007). MethodsTotally eleven genome-wide association studies were applied to search for significant genetic variants. ResultsWe found 5 different loci associated with type 2 diabetic retinopathy in or nearest gene EYA2, MPDZ, NTNG1, CTAGE14P and MREGP1. In the primary GWAS, a significant SNP rs6066146 located in gene EYA2 showed a p value of 4.21 x 10-8 and may play a role in the development of the disease, with "spleen" reaching a significant level produced by tissue expression analysis. Corresponding heritability of DR was estimated to be 26.73% by SumHer. Among five genes, we found that genes EYA2, MPDZ, NTNG1 had genetic interactions and may affect the complex development of retinal blood vessels. ConclusionDiabetic retinopathy is a complication of diabetes that affects the eyes. It is highly likely to occur when high blood sugar damages the retinal blood vessels. There is limited awareness regarding the pathogenesis of DR. Our study identified multiple loci associated with diabetic retinopathy, which may lead to personalized treatments to reduce the burden of the disease.

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