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

Simon Haworth, Dmitry Shungin, Justin T. van der Tas, Strahinja Vucic, Carolina Medina-Gomez, Victor Yakimov, Bjarke Feenstra, John R. Shaffer, Myoung Keun Lee, Marie Standl, Elisabeth Thiering, Klaus Bonnelykke, Johannes Waage, Leon Eyrich Jessen, Pia Elisabeth Norrisgaard, Raimo Joro, Ilkka Seppala, Olli Raitakari, Tom Dudding, Olja GrgicEdwin Ongkosuwito, Anu Vierola, Aino-Maija Eloranta, Nicola X. West, Steven J. Thomas, Daniel W. McNeil, Steven M. Levy, Rebecca Slayton, Ellen A. Nohr, Terho Lehtimaki, Timo Lakka, Hans Bisgaard, Jan Kuehnisch, Mary L. Marazita, Mads Melbye, Frank Geller, Fernando Rivadeneira, Eppo B. Wolvius, Paul W. Franks, Ingegerd Johansson, Nicholas J. Timpson

Research output: Contribution to journalArticleResearchpeer-review

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 [h(2) of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h(2) 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.

Original languageEnglish
Pages (from-to)3113-3127
Number of pages15
JournalHuman molecular genetics
Volume27
Issue number17
DOIs
Publication statusPublished - Sep 2018

Keywords

  • 6-YEAR-OLD CHILDREN
  • ASSOCIATION SCAN
  • CELL-MIGRATION
  • COHORT
  • HEALTH
  • HERITABILITY
  • IDENTIFICATION
  • LD SCORE REGRESSION
  • PIT-AND-FISSURE
  • POPULATIONS

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