{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:38:59Z","timestamp":1790948339345,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL146401"],"award-info":[{"award-number":["R01HL146401"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Yet despite recent advances, the genetic basis of SGS remains poorly understood. We sought to identify candidate risk genes associated with an SGS phenotype, investigate their biological function, and identify the cell types enriched for their expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Online Mendelian Inheritance in Man (OMIM) database was queried for single gene variants associated with an SGS phenotype. The functional intersections and molecular roles of the identified genes were explored using pathway enrichment analysis (PEA) computational methods. Cellular localization of the candidate risk genes was measured via transcriptional quantification in an established single cell RNA sequencing (scRNA\u2010seq) atlas of the proximal airway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty genes associated with SGS phenotype were identified. PEA resulted in 24 significantly enriched terms including \u201ccellular response to TGF\u2010\u03b2,\u201d \u201cepithelial\u2010to\u2010mesenchymal transition,\u201d and \u201cadherens junctions.\u201d Mapping the 20 candidate risk genes to the scRNA\u2010seq atlas found 3 (15%) genes were enriched in epithelial cells, 3 (15%) in fibroblasts, and 3 (15%) in endothelial cells. 11 (55%) genes were expressed ubiquitously among tissue types. Interestingly, immune cells were not significantly enriched for candidate risk genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identify and provide biologic context for 20 genes associated with fibrotic disease of the proximal airway and form the foundation for future detailed genetic study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of evidence<\/jats:title><jats:p>N\/A <jats:italic>Laryngoscope<\/jats:italic>, 133:3049\u20133056, 2023<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30718","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T08:10:54Z","timestamp":1682583054000},"page":"3049-3056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mapping Genetic Susceptibility to Stenosis in the Proximal Airway"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-212X","authenticated-orcid":false,"given":"Kayvon","family":"Sharif","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine  Nashville Tennessee U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Tierney","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery Vanderbilt University Medical Center  Nashville Tennessee U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery Vanderbilt University Medical Center  Nashville Tennessee U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wohler","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara","family":"Sobreira","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"Hillel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland 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