GWAS reveals loci associated with velopharyngeal dysfunction

• Type of Material: Article
• Authors: Jonathan Chernus, University of Pittsburgh; Jasmien Roosenboom, University of Pittsburgh; Matthew Ford, Children's Hospital of Pittsburgh; Myoung Keun Lee, University of Pittsburgh; Beth Emanuele, University of Pittsburgh; Joel Anderton, University of Pittsburgh; Jacqueline T. Hecht, McGovern Medical School and School of Dentistry UT Health at Houston; Carmencita Padilla, University of the Philippines Manila; Frederic W.B. Deleyiannis, University of Colorado; Carmen J. Buxo, University of Puerto Rico; Eleanor Feingold, University of Pittsburgh; Elizabeth Leslie, Emory University; John R. Shaffer, University of Pittsburgh; Seth M. Weinberg, University of Pittsburgh; Mary L. Marazita, University of Pittsburgh
• Language: English
• Date: 2018-05-31
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-018-26880-w
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 8
• Issue: 1
• Start Page: 8470
• End Page: 8470
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health (X01-HG00784 [MLM, EF], R01-DE016148 [MLM, SMW], R21-DE016930 [MLM], R00-DE025060 [EJL], K99-DE024571 [CJB], S21-MD001830 [CJB], U54-MD007587 [CJB].; Additional support provided by: an intramural grant from the Research Institute of the Children’s Hospital of Colorado [FWD]; operating cost support in the Philippines was provided by the Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila [CP].; Genotyping and data cleaning was provided via a contract to the Center for Inherited Disease Research: HHSN268201200008I.
• Keywords: Science & Technology - Other Topics; LIP; OROFACIAL CLEFTS; Multidisciplinary Sciences; GENES; VARIANTS; GENOME-WIDE ASSOCIATION; GRHL3; INSUFFICIENCY; CLEFT-PALATE; PHENOTYPE; REGION; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

Velopharyngeal dysfunction (VPD) occurs when the muscular soft palate (velum) and lateral pharyngeal walls are physically unable to separate the oral and nasal cavities during speech production leading to hypernasality and abnormal speech reduction. Because VPD is often associated with overt or submucous cleft palate, it could be present as a subclinical phenotype in families with a history of orofacial clefting. A key assumption to this model is that the overt and subclinical manifestations of the orofacial cleft phenotype exist on a continuum and therefore share common etiological factors. We performed a genome-wide association study in 976 unaffected relatives of isolated CP probands, 54 of whom had VPD. Five loci were significantly (p < 5 × 10-8) associated with VPD: 3q29, 9p21.1, 12q21.31, 16p12.3 and 16p13.3. An additional 15 loci showing suggestive evidence of association with VPD were observed. Several genes known to be involved in orofacial clefting and craniofacial development are located in these regions, such as TFRC, PCYT1A, BNC2 and FREM1. Although further research is necessary, this could be an indication for a potential shared genetic architecture between VPD and cleft palate, and supporting the hypothesis that VPD is a subclinical phenotype of orofacial clefting.