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This association could be partly explained by a common genetic basis; however, the genetic component of D<jats:sub>f<\/jats:sub> is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of D<jats:sub>f<\/jats:sub> and analyse its relationship with CAD. We replicated 5 D<jats:sub>f<\/jats:sub> loci and found 4 additional loci with suggestive significance (<jats:italic>P<\/jats:italic>\u2009&lt;\u20091e\u221205) to contribute to D<jats:sub>f<\/jats:sub> variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between D<jats:sub>f<\/jats:sub> and CAD, and between D<jats:sub>f<\/jats:sub> and myocardial infarction (MI), one of CAD\u2019s fatal outcomes. Fine-mapping of D<jats:sub>f<\/jats:sub> loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, D<jats:sub>f<\/jats:sub>, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC\u2009=\u20090.770\u2009\u00b1\u20090.001) when comparing with an established risk model, SCORE, (AUC\u2009=\u20090.741\u2009\u00b1\u20090.002) and extensions thereof leveraging the PRS (AUC\u2009=\u20090.728\u2009\u00b1\u20090.001). This evidences that D<jats:sub>f<\/jats:sub> provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of D<jats:sub>f<\/jats:sub>, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.<\/jats:p>","DOI":"10.1038\/s42003-023-04836-9","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T12:17:04Z","timestamp":1684153024000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-178X","authenticated-orcid":false,"given":"Ana","family":"Villaplana-Velasco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2984-8366","authenticated-orcid":false,"given":"Marie","family":"Pigeyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Engelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0010-370X","authenticated-orcid":false,"given":"Konrad","family":"Rawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Canela-Xandri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Tochel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Lona-Durazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-1482","authenticated-orcid":false,"given":"Muthu Rama Krishnan","family":"Mookiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Doney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2057-8577","authenticated-orcid":false,"given":"Esteban J.","family":"Parra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-0794","authenticated-orcid":false,"given":"Emanuele","family":"Trucco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-0086","authenticated-orcid":false,"given":"Tom","family":"MacGillivray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2384-7568","authenticated-orcid":false,"given":"Kristiina","family":"Rannikmae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-4475","authenticated-orcid":false,"given":"Albert","family":"Tenesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erola","family":"Pairo-Castineira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-3756","authenticated-orcid":false,"given":"Miguel O.","family":"Bernabeu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"4836_CR1","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","volume":"76","author":"GA Roth","year":"2020","unstructured":"Roth, G. 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