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

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

Author information

1
Medical Research Council Integrative Epidemiology Unit at Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
2
Department of Odontology, Umeå University, Umeå 901 87, Sweden.
3
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
4
Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics.
5
The Generation R Study Group.
6
Department of Internal Medicine.
7
Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3015 CN, The Netherlands.
8
Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark.
9
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
10
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
11
Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg D-85764, Germany.
12
Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich Medical Center, Munich 80337, Germany.
13
Division of Obstetrics and Gynaecology, The University of Western Australia, Perth WA 6009, Australia.
14
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, Denmark.
15
Institute of Biomedicine, School of Medicine, University of Eastern Finland Kuopio Campus, 70211 Kuopio, Finland.
16
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center Tampere - Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33520, Finland.
17
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
18
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
19
Bristol Dental School, University of Bristol, Bristol BS1 2LY, UK.
20
Department of Psychology, Eberly College of Arts and Sciences, West Virginia University, Morgantown, WA 26506-6286, USA.
21
Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Cedar Rapids, IA 52242-1010, USA.
22
Department of Pediatric Dentistry (Retired), School of Dentistry, University of Washington, Seattle, WA 98195, USA.
23
Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense 5000, Denmark.
24
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio 70210, Finland.
25
Kuopio Research Institute of Exercise Medicine, Kuopio 70100, Finland.
26
Department of Conservative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians-Universität München, Munich 80336, Germany.
27
Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark.
28
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
29
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 202 13, Sweden.
30
Department of Public Health and Clinical Medicine, Umeå University, Umeå 901 85, Sweden.
31
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.

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.

PMID:
29931343
PMCID:
PMC6097157
DOI:
10.1093/hmg/ddy237
[Indexed for MEDLINE]
Free PMC Article

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