{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:26Z","timestamp":1791928886613,"version":"4.3.4"},"reference-count":44,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"4","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2025,4,22]]},"DOI":"10.1167\/iovs.66.4.62","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T11:30:26Z","timestamp":1745321426000},"page":"62","source":"Crossref","is-referenced-by-count":1,"title":["Iris Pigmented Lesions: Unraveling the Genetic Basis of Iris Freckles and Nevi"],"prefix":"10.1167","volume":"66","author":[{"given":"Julia","family":"Boldu-Roig","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Catalan Retina Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sorli-Clemente","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Castell\u00f3n General University Hospital, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Kuljuh-Causevic","sequence":"additional","affiliation":[{"name":"Department of Medicine, Jaume I University of Castell\u00f3n, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Loras","sequence":"additional","affiliation":[{"name":"Department of Medicine, Jaume I University of Castell\u00f3n, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Catalan Retina Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrado","family":"Martinez-Cadenas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Jaume I University of Castell\u00f3n, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"11","key":"bib1","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1038\/15713","article-title":"The human eye: structure and function","volume":"5","author":"Land","year":"1999","journal-title":"Nat Med"},{"key":"bib2","first-page":"581","article-title":"Iris pigmentation and pigmented lesions: an ultrastructural study","volume":"86","author":"Eagle","year":"1988","journal-title":"Trans Am Ophthalmol Soc"},{"issue":"29","key":"bib3","doi-asserted-by":"publisher","first-page":"e2200914119","DOI":"10.1073\/pnas.2200914119","article-title":"Cell atlas of the human ocular anterior segment: tissue-specific and shared cell types","volume":"119","author":"van Zyl","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"bib4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1001\/archopht.1996.01100130433014","article-title":"Melanocytes and iris color. Light microscopic findings","volume":"114","author":"Wilkerson","year":"1996","journal-title":"Arch Ophthalmol"},{"issue":"5","key":"bib5","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1755-148X.2009.00606.x","article-title":"Genetics of human iris colour and patterns","volume":"22","author":"Sturm","year":"2009","journal-title":"Pigment Cell Melanoma Res"},{"issue":"1","key":"bib6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1136\/bjo.88.1.36","article-title":"Association between posterior uveal melanoma and iris freckles, iris naevi, and choroidal naevi","volume":"88","author":"Harbour","year":"2004","journal-title":"Br J Ophthalmol"},{"issue":"1","key":"bib7","doi-asserted-by":"publisher","first-page":"150424","DOI":"10.1098\/rsos.150424","article-title":"Analysis of iris surface features in populations of diverse ancestry","volume":"3","author":"Edwards","year":"2016","journal-title":"R Soc Open Sci"},{"issue":"5","key":"bib8","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1136\/bjophthalmol-2014-305849","article-title":"New insights into oculodermal nevogenesis and proposal for a new iris nevus classification","volume":"99","author":"Schwab","year":"2015","journal-title":"Br J Ophthalmol"},{"issue":"5","key":"bib9","doi-asserted-by":"publisher","first-page":"R192","DOI":"10.1016\/j.cub.2009.01.027","article-title":"Eye color and the prediction of complex phenotypes from genotypes","volume":"19","author":"Liu","year":"2009","journal-title":"Curr Biol"},{"issue":"5","key":"bib10","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/j.1442-9071.2010.02487.x","article-title":"Classification of iris colour: review and refinement of a classification schema","volume":"39","author":"Mackey","year":"2011","journal-title":"Clin Exp Ophthalmol"},{"issue":"3","key":"bib11","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.fsigen.2010.02.004","article-title":"IrisPlex: a sensitive DNA tool for accurate prediction of blue and brown eye colour in the absence of ancestry information","volume":"5","author":"Walsh","year":"2011","journal-title":"Forensic Sci Int Genet"},{"issue":"7","key":"bib12","doi-asserted-by":"publisher","first-page":"e542","DOI":"10.1111\/jdv.18015","article-title":"The iris clue: blue-grey periphery, blue collarette and absence of freckles predict risk of skin cancer in a Northern European population","volume":"36","author":"Ridge","year":"2022","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"5","key":"bib13","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1111\/bjd.16323","article-title":"Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case\u2013control study","volume":"178","author":"Laino","year":"2018","journal-title":"Br J Dermatol"},{"issue":"1","key":"bib14","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s40942-024-00575-z","article-title":"A potential biomarker for age-related macular degeneration disease: iris freckles","volume":"10","author":"Koc","year":"2024","journal-title":"Int J Retina Vitreous"},{"issue":"6","key":"bib15","doi-asserted-by":"publisher","first-page":"BIO174","DOI":"10.1167\/iovs.17-21751","article-title":"Iris freckles a potential biomarker for chronic sun damage","volume":"58","author":"Schwab","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib16","first-page":"250","article-title":"Pigment freckles of the iris (benign melanomas): their significance in relation to malignant melanoma of the uvea","volume":"41","author":"Reese","year":"1943","journal-title":"Trans Am Ophthalmol Soc"},{"issue":"2","key":"bib17","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.ajhg.2011.07.011","article-title":"GWAS findings for human iris patterns: associations with variants in genes that influence normal neuronal pattern development","volume":"89","author":"Larsson","year":"2011","journal-title":"Am J Hum Genet"},{"issue":"4","key":"bib18","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/ajhb.21183","article-title":"Iris texture traits show associations with iris color and genomic ancestry","volume":"23","author":"Quillen","year":"2011","journal-title":"Am J Hum Biol"},{"issue":"11","key":"bib19","doi-asserted-by":"publisher","first-page":"eabd1239","DOI":"10.1126\/sciadv.abd1239","article-title":"Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color","volume":"7","author":"Simcoe","year":"2021","journal-title":"Sci Adv"},{"issue":"6","key":"bib20","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1007\/s00414-021-02645-5","article-title":"Searching for improvements in predicting human eye colour from DNA","volume":"135","author":"Kukla-Bartoszek","year":"2021","journal-title":"Int J Legal Med"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.fsigen.2017.11.013","article-title":"Genetic determinants of freckle occurrence in the Spanish population: towards ephelides prediction from human DNA samples","volume":"33","author":"Hernando","year":"2018","journal-title":"Forensic Sci Int Genet"},{"issue":"12","key":"bib22","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1038\/ng.2007.13","article-title":"Genetic determinants of hair, eye and skin pigmentation in Europeans","volume":"39","author":"Sulem","year":"2007","journal-title":"Nat Genet"},{"issue":"6","key":"bib23","doi-asserted-by":"publisher","first-page":"e1000993","DOI":"10.1371\/journal.pgen.1000993","article-title":"Web-based, participant-driven studies yield novel genetic associations for common traits","volume":"6","author":"Eriksson","year":"2010","journal-title":"PLoS Genet"},{"issue":"1","key":"bib24","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1038\/s41467-018-04086-y","article-title":"Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure","volume":"9","author":"Visconti","year":"2018","journal-title":"Nat Commun"},{"issue":"3","key":"bib25","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1111\/pcmr.12232","article-title":"Sun-induced freckling: ephelides and solar lentigines","volume":"27","author":"Praetorius","year":"2014","journal-title":"Pigment Cell Melanoma Res"},{"issue":"4","key":"bib26","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.fsigen.2013.03.007","article-title":"Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2\/OCA2 genotype and the IrisPlex model","volume":"7","author":"Martinez-Cadenas","year":"2013","journal-title":"Forensic Sci Int Genet"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1016\/j.fsigen.2013.10.002","article-title":"Gender and eye colour prediction discrepancies: a reply to criticisms","volume":"9","author":"Martinez-Cadenas","year":"2014","journal-title":"Forensic Sci Int Genet"},{"issue":"3","key":"bib28","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.fsigen.2011.07.009","article-title":"DNA-based eye colour prediction across Europe with the IrisPlex system","volume":"6","author":"Walsh","year":"2012","journal-title":"Forensic Sci Int Genet"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.fsigen.2019.07.012","article-title":"DNA-based predictive models for the presence of freckles","volume":"42","author":"Kukla-Bartoszek","year":"2019","journal-title":"Forensic Sci Int Genet"},{"issue":"16","key":"bib30","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1093\/hmg\/10.16.1701","article-title":"The melanocortin-1-receptor gene is the major freckle gene","volume":"10","author":"Bastiaens","year":"2001","journal-title":"Hum Mol Genet"},{"issue":"1","key":"bib31","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ajhg.2010.05.017","article-title":"IRF4 variants have age-specific effects on nevus count and predispose to melanoma","volume":"87","author":"Duffy","year":"2010","journal-title":"Am J Hum Genet"},{"issue":"2","key":"bib32","doi-asserted-by":"publisher","first-page":"e135","DOI":"10.1111\/jdv.16869","article-title":"MC1R variants in relation to naevi in melanoma cases and controls: a pooled analysis from the M-SKIP project","volume":"35","author":"Stefanaki","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13293-016-0070-1","article-title":"Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin","volume":"7","author":"Hernando","year":"2016","journal-title":"Biol Sex Differ"},{"issue":"3","key":"bib34","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.jdermsci.2016.09.004","article-title":"Sex and MC1R variants in human pigmentation: differences in tanning ability and sensitivity to sunlight between sexes","volume":"84","author":"Hernando","year":"2016","journal-title":"J Dermatol Sci"},{"issue":"4","key":"bib35","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s00414-016-1388-2","article-title":"Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics","volume":"130","author":"Pospiech","year":"2016","journal-title":"Int J Legal Med"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.fsigen.2014.02.002","article-title":"The effect of gender on eye colour variation in European populations and an evaluation of the IrisPlex prediction model","volume":"11","author":"Pietroni","year":"2014","journal-title":"Forensic Sci Int Genet"},{"issue":"10","key":"bib37","doi-asserted-by":"publisher","first-page":"4507","DOI":"10.1167\/iovs.06-0391","article-title":"Uveal melanocytes do not respond to or express receptors for alpha-melanocyte-stimulating hormone","volume":"47","author":"Li","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"9","key":"bib38","first-page":"1951","article-title":"Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients","volume":"42","author":"Metzelaar-Blok","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"10","key":"bib39","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1038\/sj.bjc.6601358","article-title":"Role of MC1R variants in uveal melanoma","volume":"89","author":"Hearle","year":"2003","journal-title":"Br J Cancer"},{"issue":"R1","key":"bib40","doi-asserted-by":"publisher","first-page":"R9","DOI":"10.1093\/hmg\/ddp003","article-title":"Molecular genetics of human pigmentation diversity","volume":"18","author":"Sturm","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"5","key":"bib41","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.cell.2013.10.022","article-title":"A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF\/TFAP2A pathway","volume":"155","author":"Praetorius","year":"2013","journal-title":"Cell"},{"issue":"5","key":"bib42","doi-asserted-by":"publisher","first-page":"e1000074","DOI":"10.1371\/journal.pgen.1000074","article-title":"A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation","volume":"4","author":"Han","year":"2008","journal-title":"PLoS Genet"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"31191","DOI":"10.1038\/srep31191","article-title":"Genetic markers of pigmentation are novel risk loci for uveal melanoma","volume":"6","author":"Ferguson","year":"2016","journal-title":"Sci Rep"},{"issue":"3","key":"bib44","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.ophtha.2024.09.001","article-title":"Survival in patients with uveal melanoma is linked to genetic variation at HERC2 single nucleotide polymorphism rs12913832","volume":"132","author":"Gelmi","year":"2025","journal-title":"Ophthalmology"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:09Z","timestamp":1791927129000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.4.62","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4,22]]}}}