{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:05:28Z","timestamp":1792137928618,"version":"4.4.0"},"reference-count":38,"publisher":"Ubiquity Press, Ltd.","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIHR Cambridge Biomedical Research Centre","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82171085"],"award-info":[{"award-number":["82171085"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["gh"],"abstract":"<jats:p>Background: Cardiovascular diseases (CVDs) are the leading global cause of mortality and disability, with prevalence increasing due to aging and risk factors like obesity and hypertension. The retina, rich in microvasculature, provides a unique opportunity to investigate microvascular dysfunction linked to CVDs and other systemic vascular diseases.\nMethod: This study used a multifaceted approach to assess the genetic correlation and causal relationship between retinal characteristics and CVDs. Linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) analyses were conducted using genome-wide association study (GWAS) data from the UK Biobank and FinnGen datasets. A cross-sectional study was also conducted to validate the findings, collecting optical coherence tomography (OCT) images from 124 eyes (89 with CVDs and 35 healthy controls). A prediction model is based on least absolute shrinkage and selection operator (LASSO) regression to assess the risk of CVD.\nResult: Using LDSC and two-sample MR, we found genetic evidence consistent with a causal effect whereby genetically proxied thinner retinal nerve fiber layer (RNFL) was associated with higher risks of hypertension and myocardial infarction (MI), while genetically proxied thicker photoreceptor inner segment\/outer segment (PR-IS\/OS) was associated with coronary heart disease and MI (false discovery rate [FDR] thresholds as reported). Genetically proxied thinner retinal pigment epithelium (RPE) showed an inverse association with stroke risk. Several circulating biomarkers\u2014including lipoprotein(a) [Lp(a)], low-density lipoprotein cholesterol (LDL-C), and ApoB\u2014exhibited MR evidence of association with multiple CVDs. In a cross-sectional cohort, retinal layer differences and their relationships with lipids were directionally consistent with the genetic findings.\nConclusion: Retinal structural traits measured by OCT\u2014particularly RNFL, PR-IS\/OS, and RPE thickness\u2014are best interpreted as non-invasive markers that reflect systemic vascular biology. Our MR analyses support shared etiologic pathways between retinal microstructure and CVDs rather than implying that retinal damage clinically causes cardiovascular events. Findings warrant validation in larger and more diverse populations and should not be considered definitive proof of causality.<\/jats:p>","DOI":"10.5334\/gh.1493","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:21:44Z","timestamp":1763716904000},"page":"104","source":"Crossref","is-referenced-by-count":4,"title":["Causal Effects Between Retinal Characteristics and Cardiovascular Diseases: Insights from Genetic Correlation, Mendelian Randomization, and Cross-Sectional Study"],"prefix":"10.5334","volume":"20","author":[{"given":"Xuehao","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6406-4503","authenticated-orcid":false,"given":"Chao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-3167","authenticated-orcid":false,"given":"Dejia","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6132-0923","authenticated-orcid":false,"given":"Jishan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0641-2797","authenticated-orcid":false,"given":"Xiaorong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3285","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"issue":"2","key":"key20251121092133_B1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41569-019-0244-8","article-title":"Counter-regulatory 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