Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

Cole A Weaver; Steven F Miller; Clarissa S G da Fontoura; George L Wehby; Brad A Amendt; Nathan E Holton; Veeratrishul Allareddy; Thomas E Southard; Lina M Moreno Uribe

doi:10.1016/j.ajodo.2016.08.027

Back

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

Journal article

Peer reviewed

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

Cole A Weaver, Steven F Miller, Clarissa S G da Fontoura, George L Wehby, Brad A Amendt, Nathan E Holton, Veeratrishul Allareddy, Thomas E Southard and Lina M Moreno Uribe

American journal of orthodontics and dentofacial orthopedics, Vol.151(3), pp.539-558

03/2017

DOI: 10.1016/j.ajodo.2016.08.027

PMCID: PMC5358674

PMID: 28257739

View Online

Abstract

Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1AJUBA, SNAI3SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified.

Phenotype

Reproducibility of Results

Genetic Association Studies

Humans

Middle Aged

Malocclusion - genetics

Genotype

Male

Cone-Beam Computed Tomography

Adolescent

Adult

Female

Aged

Child

Principal Component Analysis

Anatomic Landmarks

Details

Title: Subtitle: Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion
Creators: Cole A Weaver - Private practice, Cheyenne, Wyo
Steven F Miller - Department of Anatomy, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Ill; Department of Dental Medicine, College of Dental Medicine-Illinois, Midwestern University, Downers Grove, Ill
Clarissa S G da Fontoura - The Iowa Institute for Oral and Craniofacial Research, College of Dentistry, University of Iowa, Iowa City, Iowa
George L Wehby - Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, Iowa
Brad A Amendt - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Nathan E Holton - Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa
Veeratrishul Allareddy - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa
Thomas E Southard - Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa
Lina M Moreno Uribe - The Iowa Institute for Oral and Craniofacial Research, College of Dentistry, University of Iowa, Iowa City, Iowa; Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa. Electronic address: lina-moreno@uiowa.edu
Resource Type: Journal article
Publication Details: American journal of orthodontics and dentofacial orthopedics, Vol.151(3), pp.539-558
DOI: 10.1016/j.ajodo.2016.08.027
PMID: 28257739
PMCID: PMC5358674
NLM abbreviation: Am J Orthod Dentofacial Orthop
ISSN: 0889-5406
eISSN: 1097-6752
Publisher: United States
Grant note: R90 DE024296 / NIDCR NIH HHS T32 DE014678 / NIDCR NIH HHS T90 DE023520 / NIDCR NIH HHS UL1 TR000442 / NCATS NIH HHS
Language: English
Date published: 03/2017
Academic Unit: Preventive and Community Dentistry; Radiology; Orthodontics; Anthropology; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Health Management and Policy; Economics; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
Record Identifier: 9983984545302771

Metrics

32 Record Views

16 Times Cited - Web of Science