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Genome-wide association scan for childhood caries implicates novel genes

Shaffer, JR and Wang, X and Feingold, E and Lee, M and Begum, F and Weeks, DE and Cuenco, KT and Barmada, MM and Wendell, SK and Crosslin, DR and Laurie, CC and Doheny, KF and Pugh, EW and Zhang, Q and Feenstra, B and Geller, F and Boyd, HA and Zhang, H and Melbye, M and Murray, JC and Weyant, RJ and Crout, R and McNeil, DW and Levy, SM and Slayton, RL and Willing, MC and Broffitt, B and Vieira, AR and Marazita, ML (2011) Genome-wide association scan for childhood caries implicates novel genes. Journal of Dental Research, 90 (12). 1457 - 1462. ISSN 0022-0345

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Abstract

Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries. © 2011 International & American Associations for Dental Research.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shaffer, JRjohn.r.shaffer@pitt.eduJRS51
Wang, X
Feingold, Efeingold@pitt.eduFEINGOLD
Lee, M
Begum, F
Weeks, DEweeks@pitt.eduWEEKS0000-0001-9410-7228
Cuenco, KT
Barmada, MMbarmada@pitt.eduBARMADA
Wendell, SKwend0017@pitt.eduWEND0017
Crosslin, DR
Laurie, CC
Doheny, KF
Pugh, EW
Zhang, Q
Feenstra, B
Geller, F
Boyd, HA
Zhang, H
Melbye, M
Murray, JC
Weyant, RJrjw1@pitt.eduRJW10000-0002-5252-9120
Crout, R
McNeil, DW
Levy, SM
Slayton, RL
Willing, MC
Broffitt, B
Vieira, ARarv11@pitt.eduARV11
Marazita, MLmarazita@pitt.eduMARAZITA
Date: 1 December 2011
Date Type: Publication
Journal or Publication Title: Journal of Dental Research
Volume: 90
Number: 12
Page Range: 1457 - 1462
DOI or Unique Handle: 10.1177/0022034511422910
Schools and Programs: School of Dental Medicine > Dental Science
Refereed: Yes
ISSN: 0022-0345
MeSH Headings: Child; Child, Preschool; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 17; Dental Caries--genetics; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; HapMap Project; Humans; Polymorphism, Single Nucleotide; United States
Other ID: NLM PMC3215757 [Available on 12/01/12]
PubMed Central ID: PMC3215757
PubMed ID: 21940522
Date Deposited: 24 Sep 2012 19:18
Last Modified: 20 Feb 2020 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/14351

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