Genome-wide association Scan of dental caries in the permanent dentition
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Wang, Xiaojing, et al. Genome-wide Association Scan of Dental Caries In the Permanent Dentition. BioMed Central Ltd, 2012. https://doi.org/10.17615/bv9h-2b95APA
Wang, X., Shaffer, J., Zeng, Z., Begum, F., Vieira, A., Noel, J., Anjomshoaa, I., Cuenco, K., Lee, M., Beck, J., Boerwinkle, E., Cornelis, M., Hu, F., Crosslin, D., Laurie, C., Nelson, S., Doheny, K., Pugh, E., Polk, D., Weyant, R., Crout, R., Mc Neil, D., Weeks, D., Feingold, E., & Marazita, M. (2012). Genome-wide association Scan of dental caries in the permanent dentition. BioMed Central Ltd. https://doi.org/10.17615/bv9h-2b95Chicago
Wang, Xiaojing, John R Shaffer, Zhen Zeng, Ferdouse Begum, Alexandre R Vieira, Jacqueline Noel, Ida Anjomshoaa et al. 2012. Genome-Wide Association Scan of Dental Caries In the Permanent Dentition. BioMed Central Ltd. https://doi.org/10.17615/bv9h-2b95- Creator
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Wang, Xiaojing
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
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Shaffer, John R
- Other Affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh
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Zeng, Zhen
- Other Affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh
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Begum, Ferdouse
- Other Affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh
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Vieira, Alexandre R
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh
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Noel, Jacqueline
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
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Anjomshoaa, Ida
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
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Cuenco, Karen T
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
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Lee, Myoung-Keun
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
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Beck, James
- Affiliation: School of Dentistry
- Other Affiliation: North Carolina Oral Health Institute
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Boerwinkle, Eric
- Other Affiliation: IMM Center for Human Genetics and Division of Epidemiology, School of Public Health, University of Texas, Houston
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Cornelis, Marilyn C
- Other Affiliation: Department of Nutrition, Harvard School of Public Health
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Hu, Frank B
- Other Affiliation: Department of Nutrition, Harvard School of Public Health
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Crosslin, David R
- Other Affiliation: Department of Biostatistics, University of Washington
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Laurie, Cathy C
- Other Affiliation: Department of Biostatistics, University of Washington
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Nelson, Sarah C
- Other Affiliation: Department of Biostatistics, University of Washington
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Doheny, Kimberly F
- Other Affiliation: Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore
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Pugh, Elizabeth W
- Other Affiliation: Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore
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Polk, Deborah E
- Other Affiliation: Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine
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Weyant, Robert J
- Other Affiliation: Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine
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Crout, Richard
- Other Affiliation: Department of Periodontics, West Virginia University School of Dentistry
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McNeil, Daniel W
- Other Affiliation: Dental Practice and Rural Health, West Virginia University School of Dentistry
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Weeks, Daniel E
- Other Affiliation: Department of Human Genetics, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh
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Feingold, Eleanor
- Other Affiliation: Department of Human Genetics, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh
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Marazita, Mary L
- Other Affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh
- 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.
- Date of publication
- December 21, 2012
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Xiaojing Wang et al.; licensee BioMed Central Ltd.
- License
- Journal title
- BMC Oral Health
- Journal volume
- 12
- Journal issue
- 1
- Page start
- 57
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1472-6831
- Bibliographic citation
- BMC Oral Health. 2012 Dec 21;12(1):57
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- July 15, 2016
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