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

Research output: Contribution to journalArticle

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. 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.

Details

Authors
  • 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
  • Carol Wang
  • Klaus Bønnelykke
  • Johannes Waage
  • Leon Eyrich Jessen
  • Pia Elisabeth Nørrisgaard
  • Raimo Joro
  • Ilkka Seppälä
  • Olli Raitakari
  • Tom Dudding
  • Olja Grgic
  • Edwin Ongkosuwito
  • Anu Vierola
  • Aino Maija Eloranta
  • Nicola X. West
  • Steven J. Thomas
  • Daniel W. McNeil
  • Steven M. Levy
  • Rebecca Slayton
  • Ellen A. Nohr
  • Terho Lehtimäki
  • Timo Lakka
  • Hans Bisgaard
  • Craig Pennell
  • Jan Kühnisch
  • Mary L. Marazita
  • Mads Melbye
  • Frank Geller
  • Fernando Rivadeneira
  • Eppo B. Wolvius
  • Ingegerd Johansson
  • Nicholas J. Timpson
Organisations
External organisations
  • University of Bristol
  • Umeå University
  • Harvard University
  • Erasmus University Medical Center
  • Danish Serum Institute, Copenhagen
  • University of Pittsburgh
  • Helmholtz Zentrum München
  • German Center for Lung Research (DZL)
  • University of Western Australia, Crawley
  • University of Copenhagen
  • University of Eastern Finland
  • University of Tampere
  • Turku University Hospital
  • University of Turku
  • University of West Virginia
  • University of Iowa
  • University of Washington
  • University of Southern Denmark
  • Kuopio University Hospital
  • Stanford University
  • Harvard T.H. Chan School of Public Health
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Environmental Health and Occupational Health
Original languageEnglish
Pages (from-to)3113-3127
JournalHuman Molecular Genetics
Volume27
Issue number17
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes