{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:37Z","timestamp":1792786177718,"version":"4.5.0"},"posted":{"date-parts":[[2025,6,28]]},"group-title":"Ophthalmology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["224643\/Z\/21\/Z"],"award-info":[{"award-number":["224643\/Z\/21\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"award":["CL-2017-06-001"],"award-info":[{"award-number":["CL-2017-06-001"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NIHR 203308"],"award-info":[{"award-number":["NIHR 203308"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/02catss52","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01EY017607"],"award-info":[{"award-number":["R01EY017607"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01EY033580"],"award-info":[{"award-number":["R01EY033580"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,12]]},"abstract":"<jats:p>The fovea is the small depression at the neurosensory retina that underlies high-resolution central vision. It is vulnerable to disease and disruption of its architecture can lead to visual disability. Foveal morphology varies substantially across individuals but the molecular causes and functional consequences of this variation remain incompletely understood. Here, we analyse six foveal morphological parameters derived from Optical Coherence Tomography (OCT) images of 39,521 UK Biobank participants. We find marked variation in foveal morphology and identify significant associations with sex and genetic ancestry. Genome-wide association studies identify 162 lead loci across the six foveal morphological parameters, implicating genes involved in pigmentation (including TYR, TSPAN10 and GPR143) and developmental patterning (including FGFR2, CYP26C1 and CYP1A1). Heritability estimates range from 29 to 43%. Foveal pit volume is associated with future risk of age-related macular degeneration (AMD) (hazard ratio 1.09, p = 0.026), a finding supported by Mendelian randomisation. These results establish foveal morphology as a highly heritable trait that is biologically linked to AMD.<\/jats:p>","DOI":"10.1101\/2025.06.27.25330434","type":"posted-content","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T17:50:13Z","timestamp":1751133013000},"source":"Crossref","is-referenced-by-count":2,"title":["Genetic insights into foveal morphology and its associations with pigmentation and age-related macular degeneration"],"prefix":"10.64898","author":[{"given":"David J.","family":"Green","sequence":"first","affiliation":[{"name":"University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Julian","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Romero-Bascones","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, Mondragon Unibertsitatea, Mondragon, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Torchia","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heer N.V.","family":"Joisher","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Boston, MA, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UK Biobank Eye and Vision Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unai","family":"Ayala","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, Mondragon Unibertsitatea, Mondragon, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maitane","family":"Barrenechea","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, Mondragon Unibertsitatea, Mondragon, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay E.","family":"Self","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme C.","family":"Black","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8314-8497","authenticated-orcid":false,"given":"Ewan","family":"Birney","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-6387","authenticated-orcid":false,"given":"Constance L.","family":"Cepko","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Boston, MA, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Carroll","sequence":"additional","affiliation":[{"name":"Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0986-4123","authenticated-orcid":false,"given":"Panagiotis I.","family":"Sergouniotis","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.27.25330434","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:00:14Z","timestamp":1791860414000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.06.27.25330434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.06.27.25330434","relation":{},"subject":[],"published":{"date-parts":[[2025,6,28]]},"subtype":"preprint"}}