Purpose To 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). Methods Totally eleven genome-wide association studies were applied to search for significant genetic variants. Results We 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. Conclusion Diabetic 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. Keywords: Diabetic retinopathy; UK Biobank; genome-wide association study; tissue expression analysis; heritability.

The authors have declared no competing interest.

This study was mainly funded by the Pioneer and Leading Goose R&D Program of Zhejiang Province 2023 with reference number 2023C04049 and Ningbo International Collaboration Program 2023 with reference number 2023H025.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Ethics Committee of the University of Nottingham, Ningbo, China.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

This research complies with all ethical standards and data privacy measures set by the UK Biobank. Detailed summary statistics data pertaining to Diabetic Retinopathy within the UK Biobank are retrievable from https://figshare.com/s/9d55aa774fb19307f7c8. Should there be any additional data pertinent to this study that are not presented within this paper or its additional files, the authors can provide such data upon reasonable request. Data is available upon publication.

https://figshare.com/s/9d55aa774fb19307f7c8