{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:46:18Z","timestamp":1791297978811,"version":"4.1.0"},"reference-count":121,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005648","name":"American Association of Orthodontists Foundation","doi-asserted-by":"publisher","award":["Orthodontic Faculty Development Fellowship Award"],"award-info":[{"award-number":["Orthodontic Faculty Development Fellowship Award"]}],"id":[{"id":"10.13039\/100005648","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Association of Orthodontists","award":["Full-Time Faculty Fellowship Award"],"award-info":[{"award-number":["Full-Time Faculty Fellowship Award"]}]},{"name":"University of Pennsylvania School of Dental Medicine","award":["Joseph and Josephine Rabinowitz Award for Excellence in Research"],"award-info":[{"award-number":["Joseph and Josephine Rabinowitz Award for Excellence in Research"]}]},{"name":"the Department of Orthodontics, University of Pennsylvania School of Dental Medicine","award":["the J. Henry O\u2019Hern Jr. Pilot Grant"],"award-info":[{"award-number":["the J. Henry O\u2019Hern Jr. Pilot Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skeletal class II and III malocclusions are craniofacial disorders that negatively impact people\u2019s quality of life worldwide. Unfortunately, the growth patterns of skeletal malocclusions and their clinical correction prognoses are difficult to predict largely due to lack of knowledge of their precise etiology. Inspired by the strong inheritance pattern of a specific type of skeletal malocclusion, previous genome-wide association studies (GWAS) were reanalyzed, resulting in the identification of 19 skeletal class II malocclusion-associated and 53 skeletal class III malocclusion-associated genes. Functional enrichment of these genes created a signal pathway atlas in which most of the genes were associated with bone and cartilage growth and development, as expected, while some were characterized by functions related to skeletal muscle maturation and construction. Interestingly, several genes and enriched pathways are involved in both skeletal class II and III malocclusions, indicating the key regulatory effects of these genes and pathways in craniofacial development. There is no doubt that further investigation is necessary to validate these recognized genes\u2019 and pathways\u2019 specific function(s) related to maxillary and mandibular development. In summary, this systematic review provides initial insight on developing novel gene-based treatment strategies for skeletal malocclusions and paves the path for precision medicine where dental care providers can make an accurate prediction of the craniofacial growth of an individual patient based on his\/her genetic profile.<\/jats:p>","DOI":"10.3390\/ijms222313037","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:19:08Z","timestamp":1638479948000},"page":"13037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Genes and Pathways Associated with Skeletal Sagittal Malocclusions: A Systematic Review"],"prefix":"10.3390","volume":"22","author":[{"given":"Elizabeth","family":"Gershater","sequence":"first","affiliation":[{"name":"Department of Biology, Muhlenberg College, Allentown, PA 18104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-6983","authenticated-orcid":false,"given":"Chenshuang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, Department of Orthodontics, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-0874","authenticated-orcid":false,"given":"Pin","family":"Ha","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hsi","family":"Chung","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, Department of Orthodontics, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipul","family":"Tanna","sequence":"additional","affiliation":[{"name":"School of Dental Medicine, Department of Orthodontics, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"},{"name":"Department of Orthodontics, College of Stomatology, Xi\u2019an Jiaotong University, 98 XiWu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-3563","authenticated-orcid":false,"given":"Zhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"School of Dentistry, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.sdentj.2017.10.002","article-title":"Comparison of popular sagittal cephalometric analyses for validity and reliability","volume":"30","author":"Qamaruddin","year":"2018","journal-title":"Saudi Dent. 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