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Sci Rep. 2018 May 31;8(1):8470. doi: 10.1038/s41598-018-26880-w.

GWAS reveals loci associated with velopharyngeal dysfunction.

Author information

1
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
2
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
3
Cleft Craniofacial Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
4
Department of Pediatrics, McGovern Medical School and School of Dentistry UT Health at Houston, Houston, TX, 77030, USA.
5
Department of Pediatrics, College of Medicine; and Institute of Human Genetics, National Institutes of Health; University of the Philippines Manila, Manila, 1101, The Philippines.
6
Department of Surgery, Plastic and Reconstructive Surgery, University of Colorado School of Medicine, Denver, CO, 80045, USA.
7
Dental and Craniofacial Genomics Core, School of Dental Medicine, University of Puerto Rico, San Juan, 00936, Puerto Rico.
8
Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, GA, 30322, USA.
9
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. smwst46@pitt.edu.
10
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA. smwst46@pitt.edu.
11
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. marazita@pitt.edu.
12
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA. marazita@pitt.edu.

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.

PMID:
29855589
PMCID:
PMC5981322
DOI:
10.1038/s41598-018-26880-w
[Indexed for MEDLINE]
Free PMC Article

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