Family-based GWAS for dental class I malocclusion and clefts.
Humans
Cleft Lip
/ genetics
Cleft Palate
/ genetics
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Female
Male
Malocclusion, Angle Class I
/ genetics
Cohort Studies
Linkage Disequilibrium
/ genetics
Child
Genotype
Adolescent
Genetic Markers
Adult
Phenotype
Multifactorial Inheritance
/ genetics
Young Adult
Class I malocclusion
Cleft lip
Cleft palate
GWAS
Genetic variation
Journal
BMC oral health
ISSN: 1472-6831
Titre abrégé: BMC Oral Health
Pays: England
ID NLM: 101088684
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
received:
25
03
2024
accepted:
04
06
2024
medline:
8
6
2024
pubmed:
8
6
2024
entrez:
7
6
2024
Statut:
epublish
Résumé
Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts. Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion. In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate. These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.
Sections du résumé
BACKGROUND
BACKGROUND
Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts.
METHODS
METHODS
Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion.
RESULTS
RESULTS
In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate.
CONCLUSIONS
CONCLUSIONS
These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.
Identifiants
pubmed: 38849772
doi: 10.1186/s12903-024-04444-x
pii: 10.1186/s12903-024-04444-x
doi:
Substances chimiques
Genetic Markers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
665Subventions
Organisme : NIH HHS
ID : R21-DE16718
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Proffit WR, Fields HW, Sarver DM. Contemporary orthodontics. 4th ed. St. Louis, Mo.: Mosby Elsevier; 2007. xii, 751 p. p.
Ghodasra R, Brizuela M, Orthodontics. Malocclusion. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Melina Brizuela declares no relevant financial relationships with ineligible companies.2023.
Rolfe S, Lee SI, Shapiro L. Associations between genetic data and quantitative Assessment of normal facial asymmetry. Front Genet. 2018;9:659.
doi: 10.3389/fgene.2018.00659
pubmed: 30631343
pmcid: 6315129
Gershater E, Li C, Ha P, Chung CH, Tanna N, Zou M et al. Genes and pathways associated with skeletal sagittal malocclusions: a systematic review. Int J Mol Sci. 2021;22(23).
Vyas T, Gupta P, Kumar S, Gupta R, Gupta T, Singh HP. Cleft of lip and palate: a review. J Family Med Prim Care. 2020;9(6):2621–5.
doi: 10.4103/jfmpc.jfmpc_472_20
pubmed: 32984097
pmcid: 7491837
Paradowska-Stolarz A, Kawala B. Occlusal disorders among patients with total clefts of lip, alveolar bone, and palate. Biomed Res Int. 2014;2014:583416.
doi: 10.1155/2014/583416
pubmed: 24982898
pmcid: 4058232
Alkhouri S, Waite PD, Davis MB, Lamani E, Kau CH. Maxillary distraction osteogenesis in unilateral cleft lip and palate patients with rigid external distraction system. Ann Maxillofac Surg. 2017;7(1):57–63.
doi: 10.4103/ams.ams_174_16
pubmed: 28713737
pmcid: 5502517
Vieira AR, Marazita ML, Goldstein-McHenry T. Genome-wide scan finds suggestive caries loci. J Dent Res. 2008;87(5):435–9.
doi: 10.1177/154405910808700506
pubmed: 18434572
O’Connell JR, Weeks DE. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998;63(1):259–66.
doi: 10.1086/301904
pubmed: 9634505
pmcid: 1377228
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75.
doi: 10.1086/519795
pubmed: 17701901
pmcid: 1950838
Floros J, Fan R, Matthews A, DiAngelo S, Luo J, Nielsen H, et al. Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences. Clin Genet. 2001;60(3):178–87.
doi: 10.1034/j.1399-0004.2001.600303.x
pubmed: 11595019
Whelan L, Dockery A, Stephenson KAJ, Zhu J, Kopcic E, Post IJM, et al. Detailed analysis of an enriched deep intronic ABCA4 variant in Irish stargardt disease patients. Sci Rep. 2023;13(1):9380.
doi: 10.1038/s41598-023-35889-9
pubmed: 37296172
pmcid: 10256698
Ahmad A, Strohbuecker S, Tufarelli C, Sottile V. Expression of a SOX1 overlapping transcript in neural differentiation and cancer models. Cell Mol Life Sci. 2017;74(22):4245–58.
doi: 10.1007/s00018-017-2580-3
pubmed: 28674729
pmcid: 5641280
da Fontoura CS, Miller SF, Wehby GL, Amendt BA, Holton NE, Southard TE, et al. Candidate gene analyses of skeletal variation in malocclusion. J Dent Res. 2015;94(7):913–20.
doi: 10.1177/0022034515581643
pubmed: 25910506
pmcid: 4530344
Zawislak A, Wozniak K, Agirre X, Gupta S, Kawala B, Znamirowska-Bajowska A et al. Association of ABCA4 gene polymorphisms with cleft lip with or without cleft palate in the polish population. Int J Environ Res Public Health. 2021;18(21).
Yuan Q, Blanton SH, Hecht JT. Association of ABCA4 and MAFB with non-syndromic cleft lip with or without cleft palate. Am J Med Genet A. 2011;155A(6):1469–71.
doi: 10.1002/ajmg.a.33940
pubmed: 21567910
Neela PK, Gosla SR, Husain A, Mohan V, Thumoju S, Bv R. Association of MAPK4 and SOX1-OT gene polymorphisms with cleft lip palate in multiplex families: a genetic study. J Dent Res Dent Clin Dent Prospects. 2020;14(2):93–6.
doi: 10.34172/joddd.2020.021
pubmed: 32908649
pmcid: 7464228
Yildirim M, Seymen F, Deeley K, Cooper ME, Vieira AR. Defining predictors of cleft lip and palate risk. J Dent Res. 2012;91(6):556–61.
doi: 10.1177/0022034512444928
pubmed: 22496123
Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, et al. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet. 2010;42(6):525–9.
doi: 10.1038/ng.580
pubmed: 20436469
pmcid: 2941216
Al-Zaid FS, Hurley MJ, Dexter DT, Gillies GE. Neuroprotective role for RORA in Parkinson’s disease revealed by analysis of post-mortem brain and a dopaminergic cell line. NPJ Parkinsons Dis. 2023;9(1):119.
doi: 10.1038/s41531-023-00563-4
pubmed: 37500636
pmcid: 10374904
Li M, Olotu J, Buxo-Martinez CJ, Mossey PA, Anand D, Busch T, et al. Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations. Oral Dis. 2022;28(7):1921–35.
doi: 10.1111/odi.13932
pubmed: 34061439
Reyes-Gibby CC, Wang J, Yeung SJ, Chaftari P, Yu RK, Hanna EY, et al. Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer. Sci Rep. 2018;8(1):8789.
doi: 10.1038/s41598-018-27070-4
pubmed: 29884837
pmcid: 5993794
Urraca N, Hope K, Victor AK, Belgard TG, Memon R, Goorha S, et al. Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons. Mol Autism. 2018;9:6.
doi: 10.1186/s13229-018-0191-y
pubmed: 29423132
pmcid: 5787244
Urraca N, Cleary J, Brewer V, Pivnick EK, McVicar K, Thibert RL, et al. The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature. Autism Res. 2013;6(4):268–79.
doi: 10.1002/aur.1284
pubmed: 23495136
pmcid: 3884762
Devlin B, Roeder K. Genomic control for association studies. Biometrics. 1999;55(4):997–1004.
doi: 10.1111/j.0006-341X.1999.00997.x
pubmed: 11315092