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. 2018 Sep 1;27(17):3113-3127.
doi: 10.1093/hmg/ddy237.

Consortium-based genome-wide meta-analysis for childhood dental caries traits

Simon Haworth  1 , Dmitry Shungin  2   3 , Justin T van der Tas  4 , Strahinja Vucic  4 , Carolina Medina-Gomez  5   6   7 , Victor Yakimov  8 , Bjarke Feenstra  8 , John R Shaffer  9   10 , Myoung Keun Lee  10 , Marie Standl  11 , Elisabeth Thiering  11   12 , Carol Wang  13 , Klaus Bønnelykke  14 , Johannes Waage  14 , Leon Eyrich Jessen  14 , Pia Elisabeth Nørrisgaard  14 , Raimo Joro  15 , Ilkka Seppälä  16 , Olli Raitakari  17   18 , Tom Dudding  1 , Olja Grgic  4   5 , Edwin Ongkosuwito  5 , Anu Vierola  15 , Aino-Maija Eloranta  15 , Nicola X West  19 , Steven J Thomas  19 , Daniel W McNeil  20 , Steven M Levy  21 , Rebecca Slayton  22 , Ellen A Nohr  23 , Terho Lehtimäki  16 , Timo Lakka  15   24   25 , Hans Bisgaard  14 , Craig Pennell  13 , Jan Kühnisch  26 , Mary L Marazita  9   10 , Mads Melbye  8   27   28 , Frank Geller  8 , Fernando Rivadeneira  5   6   7 , Eppo B Wolvius  4 , Paul W Franks  29   30   31 , Ingegerd Johansson  2 , Nicholas J Timpson  1
Affiliations

Consortium-based genome-wide meta-analysis for childhood dental caries traits

Simon Haworth et al. Hum Mol Genet. .

Abstract

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

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Figures

Figure 1.
Figure 1.
 Manhattan plots for each principal meta-analysis. (A) Caries in primary teeth (European ancestry), n samples = 17 036, n variants = 8 640 819, λ  =  0.9944. Variants within 500Kb of rs1594318 are highlighted in green. (B) Caries in primary teeth (multi-ethnic analysis), n samples = 19 003, n variants = 8 699 928, λ  = 0.9861. (C) Caries in permanent teeth (European ancestry), n samples = 13 353, n variants = 8 734 121, λ  = 0.9991. Variants within 500Kb of rs7738851 are highlighted in green.
Figure 2.
Figure 2.
 Regional association plots. (A) Regional association plot for rs1594318 and caries in primary teeth (European ancestry meta-analysis). (B) Regional association plot for rs7738851 and caries in permanent teeth.
Figure 3.
Figure 3.
 Forest plot for rs1594318 and caries in primary teeth. Effect sizes are expressed on a log OR scale, grouped by geographical location. The summary estimate is from the fixed-effect meta-analysis of participants of European ancestry.
Figure 4.
Figure 4.
 Forest plot for rs7738851 and caries in permanent teeth. Effect sizes are expressed on a log OR scale, grouped by geographical location. The summary estimate is from fixed-effect meta-analysis.
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References

    1. Kassebaum N.J., Bernabe E., Dahiya M., Bhandari B., Murray C.J.L., Marcenes W. (2015) Global burden of untreated caries: a systematic review and metaregression. J. Dent. Res., 94, 650–658. - PubMed
    1. Vernazza C.R., Rolland S.L., Chadwick B., Pitts N. (2016) Caries experience, the caries burden and associated factors in children in England, Wales and Northern Ireland 2013. Br. Dent. J., 221, 315–320. - PMC - PubMed
    1. van der Tas J.T., Kragt L., Elfrink M.E.C., Bertens L.C.M., Jaddoe V.W.V., Moll H.A., Ongkosuwito E.M., Wolvius E.B. (2017) Social inequalities and dental caries in six-year-old children from the Netherlands. J. Dentistry, 62, 18–24. - PMC - PubMed
    1. Schuller A.A., van Dommelen P., Poorterman J.H.G. (2014) Trends in oral health in young people in the Netherlands over the past 20 years: a study in a changing context. Commun. Dent. Oral Epidemiol., 42, 178–184. - PubMed
    1. Philip N., Suneja B., Walsh L.J. (2018) Ecological approaches to dental caries prevention: paradigm shift or shibboleth? Caries Res., 52, 153–165. - PubMed

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