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

Haworth, Simon; Shungin, Dmitry LU ; Van Der Tas, Justin T.; Vucic, Strahinja; Medina-Gomez, Carolina; Yakimov, Victor; Feenstra, Bjarke; Shaffer, John R.; Lee, Myoung Keun and Standl, Marie, et al. (2018) In Human Molecular Genetics 27(17). p.3113-3127
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... (More)

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. Consortiumwide 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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Human Molecular Genetics
volume
27
issue
17
pages
3113 - 3127
publisher
Oxford University Press
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  • scopus:85055418212
ISSN
0964-6906
DOI
10.1093/hmg/ddy237
language
English
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yes
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1a7e24fd-1224-4b94-8828-37e48af73f5b
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2018-12-07 15:32:31
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2019-08-14 04:29:06
@article{1a7e24fd-1224-4b94-8828-37e48af73f5b,
  abstract     = {<p>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. Consortiumwide 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.</p>},
  author       = {Haworth, Simon and Shungin, Dmitry and Van Der Tas, Justin T. and Vucic, Strahinja and Medina-Gomez, Carolina and Yakimov, Victor and Feenstra, Bjarke and Shaffer, John R. and Lee, Myoung Keun and Standl, Marie and Thiering, Elisabeth and Wang, Carol and Bønnelykke, Klaus and Waage, Johannes and Jessen, Leon Eyrich and Nørrisgaard, Pia Elisabeth and Joro, Raimo and Seppälä, Ilkka and Raitakari, Olli and Dudding, Tom and Grgic, Olja and Ongkosuwito, Edwin and Vierola, Anu and Eloranta, Aino Maija and West, Nicola X. and Thomas, Steven J. and McNeil, Daniel W. and Levy, Steven M. and Slayton, Rebecca and Nohr, Ellen A. and Lehtimäki, Terho and Lakka, Timo and Bisgaard, Hans and Pennell, Craig and Kühnisch, Jan and Marazita, Mary L. and Melbye, Mads and Geller, Frank and Rivadeneira, Fernando and Wolvius, Eppo B. and Franks, Paul W. and Johansson, Ingegerd and Timpson, Nicholas J.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {17},
  pages        = {3113--3127},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Consortium-based genome-wide meta-analysis for childhood dental caries traits},
  url          = {http://dx.doi.org/10.1093/hmg/ddy237},
  volume       = {27},
  year         = {2018},
}