Genome-wide association Scan of dental caries in the permanent dentition

Authors

Xiaojing Wang, University of Pittsburgh
John R. Schaffer, University of Pittsburgh
Zhen Zeng, University of Pittsburgh
Ferdouse Begum, University of Pittsburgh
Alexandre R. Vieira, University of Pittsburgh
Jacqueline Noel, University of Pittsburgh
Ida Anjomshoaa, University of Pittsburgh
Karen T. Cuenco, University of Pittsburgh
Myoung-Keun Lee, University of Pittsburgh
James Beck, North Carolina Oral Health Institute
Eric Boerwinkle, University of Texas at Austin
Marilyn C. Cornelis, Harvard University
Frank B. Hu, Harvard University
David R. Crosslin, University of Washington
Cathy C. Laurie, University of Washington
Sarah C. Nelson, University of Washington
Kimberly F. Doheny, The Johns Hopkins University
Elizabeth W. Pugh, The Johns Hopkins University
Deborah E. Polk, University of Pittsburgh
Robert J. Weyant, University of Pittsburgh
Richard Crout, West Virginia University
Daniel W. McNeil, West Virginia University
Daniel E. Weeks, University of Pittsburgh
Eleanor Feingold, University of Pittsburgh
Mary L. Marazita, University of Pittsburgh

Author ORCID Identifier

N/A

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https://orcid.org/0000-0001-7835-8051

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https://orcid.org/0000-0003-3658-9059

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https://orcid.org/0000-0002-2109-6465

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https://orcid.org/0000-0002-1402-4068

https://orcid.org/0000-0002-5252-9120

https://orcid.org/0000-0002-7695-5685

https://orcid.org/0000-0002-0766-8455

https://orcid.org/0000-0001-9410-7228

https://orcid.org/0000-0003-2898-6484

https://orcid.org/0000-0002-2648-2832

Document Type

Article

Publication Date

2013

College/Unit

School of Dentistry

Department/Program/Center

Medicine

Abstract

Background

Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.

Methods

Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.

Results

Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.

Conclusions

As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.

Digital Commons Citation

Wang, Xiaojing; Schaffer, John R.; Zeng, Zhen; Begum, Ferdouse; Vieira, Alexandre R.; Noel, Jacqueline; Anjomshoaa, Ida; Cuenco, Karen T.; Lee, Myoung-Keun; Beck, James; Boerwinkle, Eric; Cornelis, Marilyn C.; Hu, Frank B.; Crosslin, David R.; Laurie, Cathy C.; Nelson, Sarah C.; Doheny, Kimberly F.; Pugh, Elizabeth W.; Polk, Deborah E.; Weyant, Robert J.; Crout, Richard; McNeil, Daniel W.; Weeks, Daniel E.; Feingold, Eleanor; and Marazita, Mary L., "Genome-wide association Scan of dental caries in the permanent dentition" (2013). Faculty & Staff Scholarship. 2653.
https://researchrepository.wvu.edu/faculty_publications/2653

Source Citation

Wang, X., Shaffer, J.R., Zeng, Z. et al. Genome-wide association Scan of dental caries in the permanent dentition. BMC Oral Health 12, 57 (2012). https://doi.org/10.1186/1472-6831-12-57

Comments

© 2012 Wang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.