Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts

Details

• Alternative Title:
  Hum Hered
• Personal Author:
  Alotaibi, Rasha N. ; Howe, Brian J. ; Moreno Uribe, Lina M. ; Sanchez, Carla ; Deleyiannis, Frederic W.B. ; Padilla, Carmencita ; Poletta, Fernando A. ; Orioli, Ieda M. ; Buxó, Carmen J. ; Wehby, George L. ; Vieira, Alexandre R. ; Murray, Jeffrey ; Valencia-Ramírez, Consuelo ; Restrepo Muñeton, Claudia P. ; Long, Ross E. ; Shaffer, John R. ; Reis, Steven E. ; Weinberg, Seth M. ; Neiswanger, Katherine ; McNeil, Daniel W. ; Marazita, Mary L.
• Description:
  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 7–82 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 < 5×10−8), and many suggestive association signals (5×10−8 < P < 5×10−6) near genes with plausible roles in tooth/enamel development.
  
  Discussion/Conclusion:
  
  The strongest association signal (P = 1.57×10−9) 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.
  
  
• Subjects:
  Article Dental Anomalies Enamel Hypoplasia Genetics GWAS Multiethnic
• Source:
  Hum Hered.
• Pubmed ID:
  35172313
• Pubmed Central ID:
  PMC9378791
• Document Type:
  Journal Article
• Funding:
  R00 DE024571/DE/NIDCR NIH HHSUnited States/ ; R03 DE024264/DE/NIDCR NIH HHSUnited States/ ; U01 DE024425/DE/NIDCR NIH HHSUnited States/ ; U01 DE018903/DE/NIDCR NIH HHSUnited States/ ; R21 DE016930/DE/NIDCR NIH HHSUnited States/ ; K99 DE024571/DE/NIDCR NIH HHSUnited States/ ; R01 DD000295/DD/NCBDD CDC HHSUnited States/ ; R01 DE014899/DE/NIDCR NIH HHSUnited States/ ; U54 MD007587/MD/NIMHD NIH HHSUnited States/
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7047534f0b7522c06b1ff39176c7c1b70a7f37b4ea2dddcb0c765151a83b61b7
• Download URL:
  https://stacks.cdc.gov/view/cdc/120310/cdc_120310_DS1.pdf
• File Type:
  [PDF - 1.21 MB ]