Article open access publication

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

Human Molecular Genetics, Oxford University Press (OUP), ISSN 1460-2083

Volume 27, 17, 2018

DOI:10.1093/hmg/ddy237, Dimensions: pub.1104916693, PMC: PMC6097157, PMID: 29931343,

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  1. (1) University of Bristol, grid.5337.2
  2. (2) Broad Institute, grid.66859.34
  3. (3) Umeå University, grid.12650.30
  4. (4) Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics
  5. (5) The Generation R Study Group
  6. (6) Department of Internal Medicine
  7. (7) Erasmus University Medical Center, grid.5645.2
  8. (8) State Serum Institute, grid.6203.7
  9. (9) University of Pittsburgh, grid.21925.3d
  10. (10) Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg D-85764, Germany
  11. (11) Klinikum der Universität München, grid.411095.8
  12. (12) University of Western Australia, grid.1012.2
  13. (13) University of Copenhagen, grid.5254.6, KU
  14. (14) University of Eastern Finland, grid.9668.1
  15. (15) Tampere University, grid.502801.e
  16. (16) Turku University Hospital, grid.410552.7
  17. (17) University of Turku, grid.1374.1
  18. (18) West Virginia University, grid.268154.c
  19. (19) University of Iowa, grid.214572.7
  20. (20) University of Washington, grid.34477.33
  21. (21) University of Southern Denmark, grid.10825.3e, SDU
  22. (22) Kuopio University Hospital, grid.410705.7
  23. (23) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
  24. (24) Department of Conservative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians-Universität München, Munich 80336, Germany
  25. (25) Stanford University, grid.168010.e
  26. (26) Harvard University, grid.38142.3c
  27. (27) Lund University, grid.4514.4

Description

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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Field Citation Ratio (FCR): 3.59

Relative Citation ratio (RCR): 1

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