{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:07:40Z","timestamp":1789420060945,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (<jats:italic>OPN1LW<\/jats:italic>, <jats:italic>OPN1MW<\/jats:italic>, <jats:italic>OPN1SW<\/jats:italic>) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms.<\/jats:p><jats:p><jats:bold>Materials and Methods:<\/jats:bold> Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Concerning DP, three genes: <jats:italic>PIWIL4<\/jats:italic> (FDR-p: 9.01*10<jats:sup>\u20139<\/jats:sup>), <jats:italic>MBD2<\/jats:italic> (FDR-p: 4.97*10<jats:sup>\u20138<\/jats:sup>) and <jats:italic>NTN1<\/jats:italic> (FDR-p: 4.98*10<jats:sup>\u20138<\/jats:sup>), stood out as promising candidates. <jats:italic>PIWIL4<\/jats:italic> is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while <jats:italic>MBD2<\/jats:italic> and <jats:italic>NTN1<\/jats:italic> are both involved in visual signal transmission. With regards to TR, four genes: <jats:italic>VPS54<\/jats:italic> (FDR-p: 4.09*10<jats:sup>\u20139<\/jats:sup>), <jats:italic>IQGAP<\/jats:italic> (FDR-p: 6,52*10<jats:sup>\u201310<\/jats:sup>), <jats:italic>NMB<\/jats:italic> (FDR-p: 8.34*10<jats:sup>\u201311<\/jats:sup>), and <jats:italic>MC5R<\/jats:italic> (FDR-p: 2.10*10<jats:sup>\u20138<\/jats:sup>), were considered promising candidates. <jats:italic>VPS54<\/jats:italic> is reported to be associated with Retinitis pigmentosa; <jats:italic>IQGAP1<\/jats:italic> is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; <jats:italic>NMB<\/jats:italic> is involved in RPE homeostasis regulation; <jats:italic>MC5R<\/jats:italic> is reported to regulate lacrimal gland function.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.<\/jats:p>","DOI":"10.3389\/fgene.2023.1161696","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T04:55:08Z","timestamp":1686286508000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations"],"prefix":"10.3389","volume":"14","author":[{"given":"Giuseppe Giovanni","family":"Nardone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Spedicati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pina","family":"Concas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Santin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Mazzetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Battaglia-Parodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Girotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1074\/jbc.M603454200","article-title":"Peripheral effect of \u03b1-Melanocyte-stimulating hormone on fatty acid oxidation in skeletal muscle","volume":"282","author":"An","year":"2007","journal-title":"J. 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