Journal
JOURNAL OF DENTAL RESEARCH
Volume 90, Issue 12, Pages 1457-1462Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0022034511422910
Keywords
caries; childhood caries; fluoride(s); genetics; genome-wide association study; genomics
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Funding
- NIH [U01-DE018903, U01-HG004438, U01-HG004423, U01-HG004446, R01-DE014899, R01-DE0 9551, R01-DE12101, R03-DE021425, P60-DE-13076, HHSN268200782-096C]
- Danish NRF
- Danish Pharmacists' Fund
- Egmont Foundation
- March of Dimes
- Augustinus Foundation
- Danish Health Insurance Societies
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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.
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