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. 2018 Jun 1;18(1):98.
doi: 10.1186/s12903-018-0559-6.

Novel caries loci in children and adults implicated by genome-wide analysis of families

Manika Govil  1 , Nandita Mukhopadhyay  2 , Daniel E Weeks  3   4 , Eleanor Feingold  2   3   4 , John R Shaffer  2   3 , Steven M Levy  5   6 , Alexandre R Vieira  2   3 , Rebecca L Slayton  7 , Daniel W McNeil  8   9 , Robert J Weyant  10 , Richard J Crout  11 , Mary L Marazita  2   3   12
Affiliations

Novel caries loci in children and adults implicated by genome-wide analysis of families

Manika Govil et al. BMC Oral Health. .

Abstract

Background: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited.

Methods: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here.

Results: Multipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19.

Conclusions: These multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual's genetic risk of disease.

Keywords: Dental genetics; Dental public health; Genome-wide linkage study; Non-parametric linkage; Permanent dentition caries; Primary dentition caries.

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Conflict of interest statement

Ethics approval and consent to participate

All subject recruitment and data collection was approved by the site-specific Institutional Review Boards listed below. At each site, written consent to participate was obtained from all study subjects.

COHRA participants: University of Pittsburgh Institutional Review Board and West Virginia University Institutional Review Board.

IHS participants: University of Iowa Institutional Review Board.

IFS participants: University of Iowa Institutional Review Board.

DRDR participants: University of Pittsburgh Institutional Review Board.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Distribution of (a) PRIM by binary affection status, (b) age at exam of individuals categorized as PRIM affected, (c) raw dft + D1MFT (d) age-adjusted QTOT1, (e) age-adjusted QTOT1 for the full sample compared to the distribution for the 2–60 age group, (f) raw dft + D2MFT, (g) age-adjusted QTOT2, (h) age-adjusted QTOT2 for the full sample compared to the distribution for the 2–60 age group, and (i) mean, standard deviation, range and sample size for QTOT1 and QTOT2; shaded areas in panels D and G indicate individuals below the age of 2 and above 60 years with phenotypes excluded from quantitative trait linkage analysis
Fig. 2
Fig. 2
Genome-wide LOD scores: (a) PRIM, (b) QTOT1, (c) QTOT2. PRIM results include the X chromosome. The empirical genome-wide 0.05 significance levels are indicated in each panel with a solid (red, online) horizontal line
Fig. 3
Fig. 3
Sensitivity of QT LOD score to changes in HP. Panels (a) and (c) are for QTOT1, and (b) and (d) are for QTOT2. In each scatterplot, the x-axis represents LOD scores reported in this paper, using HP = 50%. In panels (a) and (b), the y-axis represents LOD scores for HP = 40%. In panels (c) and (d), y-axis represents LOD scores calculated with HP = 60%. Panels E and F show the proportion (%) of SNPs switching from LOD ≤ 2.0 to LOD ≥ 2.0 for QTOT1 and QTOT2
See this image and copyright information in PMC

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