Purpose: Diabetic retinopathy (DR), a complication affecting the eyes, is associated with diabetes. This study aims to identify genetic variants associated with DR in patients with type 1 diabetes in the UK Biobank cohort (n = 1,004). Methods: A genome-wide association study (GWAS) was conducted to identify significant genetic variants of DR in type 1 diabetes. The findings are set to undergo validation during the replication and meta-analysis stages by using six cohorts: African American, European, FinnGen, GoSHARE, GoDARTS and Caucasian Australians. Results: In a locus, top single nucleotide polymorphism (SNP) rs184619214 in CCDC7 reached a GWAS significance level (p = 6.38 x 10-9) and rs79853754 in ITGB1 (p = 3.24 x 10-8), with both genes being adjacent to each other. The SNP-based heritability was estimated to be 31.09%. Rs184619214 was replicated and reached statistical significance (p < 5.0 x 10-8) in the meta-analysis stage. Pathway analysis revealed that ITGB1 is involved in the generation of biomolecules that impact the progression of DR. PheWAS analysis revealed that osteoarthritis (OA) of the hip was significantly associated with most of the SNPs of the locus. Mendelian Randomization further confirmed an association between OA and DR. Conclusions: Our study has identified a novel genomic risk locus associated with DR in type 1 diabetes, located in the intergenic region between the CCDC7 and ITGB1 genes, providing insights for DR researchers. Keywords: Diabetic retinopathy; genome-wide association study; meta-analysis; Phenome-Wide Association Study; type 1 diabetes

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 adheres to all ethical guidelines and data protection protocols of the UK Biobank.This study was approved by the Ethics Committee of the University of Nottingham, Ningbo, China. The research received the necessary ethical approval from the National Health Service National Research Ethics Service (reference 11/NW/0382)

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

Detailed summary statistics data about DR within the UKB are retrievable from https://figshare.com/s/68c2e17003c694c6f453. Should any additional data pertinent to this study need to be presented within this paper or its other files, the authors can provide such data upon reasonable request.

https://figshare.com/s/68c2e17003c694c6f453