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This study aims to identify the genetic variants associated with DR in type 2 diabetes (T2D) patients from the UK Biobank cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916,988).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We conducted a genome-wide association study (GWAS) of DR and integrated genomic results with multi-omics data to identify and prioritize susceptibility variants and genes. The findings are set to undergo validation in four replication cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Here we show that the lead SNP rs6066146 in\n                      <jats:italic>EYA2<\/jats:italic>\n                      reaches genome-wide significance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.21\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) and is replicated in three independent cohorts. The SNP-based heritability for DR is estimated at 14.6% (standard deviation: 0.11). Colocalization analysis at the\n                      <jats:italic>EYA2<\/jats:italic>\n                      locus suggests moderate colocalization (PP.H4\u2009=\u20090.553) alongside distinct association signals for DR and T2D, and cis-Mendelian randomization (MR) within the\n                      <jats:italic>EYA2<\/jats:italic>\n                      region provides gene-centric evidence that T2D exerts a significant causal effect on DR. Exploratory multivariable MR identifies proinsulin as a significant mediator of T2D on DR, which may partly account for the moderate evidence for colocalization. Tissue expression, chromatin interaction, and transcriptome-wide association analyses point to the spleen, while gene set analysis identifies B-cell pathways. Together, these convergent signals suggest that splenic B-cell abundance could serve as a predictive marker for DR risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates a genomic risk locus in gene\n                      <jats:italic>EYA2<\/jats:italic>\n                      associated with DR in type 2 diabetes, which offers deeper insights into broader trait architecture on DR.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01465-1","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:16:17Z","timestamp":1771992977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A genome-wide association study identifies EYA2 as a contributing gene for diabetic retinopathy in type 2 diabetes"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-506X","authenticated-orcid":false,"given":"Tengda","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charvi","family":"Nangia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aravind L.","family":"Rajendrakumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Dottorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mainul","family":"Haque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin NA","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqing","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-8494","authenticated-orcid":false,"given":"Weihua","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"1465_CR1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.2337\/dc11-1909","volume":"35","author":"JWY Yau","year":"2012","unstructured":"Yau, J. 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