Journal article
Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts
Human heredity, Vol.87(2), pp.34-50
08/01/2022
DOI: 10.1159/000522642
PMCID: PMC9378791
PMID: 35172313
Abstract
Introduction: Enamel hypoplasia causes a reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. Methods: A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7 to 82 years. Mixed models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Results: Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (p < 5 x 10(-8)), and many suggestive association signals (5 x 10(-8) < p < 5 x 10(-6)) near genes with plausible roles in tooth/enamel development. Conclusion: The strongest association signal (p = 1.57 x 10(-9)) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.
Details
- Title: Subtitle
- Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts
- Creators
- Rasha N. Alotaibi - King Saud UniversityBrian J. Howe - University of IowaLina M. Moreno Uribe - University of IowaCarla Sanchez - University of PittsburghFrederic W. B. DeleyiannisCarmencita Padilla - University of the Philippines ManilaFernando A. Poletta - National Institute on Population Medical GeneticsIeda M. Orioli - Univ Fed Rio de Janeiro, Inst Biol, Dept Genet, Rio De Janeiro, BrazilCarmen J. Buxo - University of Puerto Rico, Medical Sciences CampusGeorge L. Wehby - University of IowaAlexandre R. Vieira - University of PittsburghJeffrey Murray - University of IowaConsuelo Valencia-Ramirez - Clin Noel Medellin, Medellin, ColombiaClaudia P. Restrepo Muneton - Clin Noel Medellin, Medellin, ColombiaRoss E. Long - Lancaster Cleft Palate Clin, Lancaster, PA USAJohn R. Shaffer - University of PittsburghSteven E. Reis - University of PittsburghSeth M. Weinberg - University of PittsburghKatherine Neiswanger - University of PittsburghDaniel W. McNeil - West Virginia UniversityMary L. Marazita - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Human heredity, Vol.87(2), pp.34-50
- DOI
- 10.1159/000522642
- PMID
- 35172313
- PMCID
- PMC9378791
- NLM abbreviation
- Hum Hered
- ISSN
- 0001-5652
- eISSN
- 1423-0062
- Publisher
- Karger
- Number of pages
- 17
- Grant note
- R01-DE016148; X01-HG007485; R01-DE014899; U01-DE018903; X01-HG009878; R21-DE016930; R03-DE024264; R01-DE015667; K99-DE024571; R25-MD007607; U54-MD007587; R01-DD000295; U01-DE024425 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA HHSN268200782096C; HHSN268201200008I / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 08/01/2022
- Academic Unit
- Preventive and Community Dentistry; Health Management and Policy; Dental Clinic Administration; Pediatric Dentistry; Craniofacial Anomalies Research Center; Family Dentistry; Orthodontics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Economics; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984367694002771
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