Journal article
Consortium-based genome-wide meta-analysis for childhood dental caries traits
Human molecular genetics, Vol.27(17), pp.3113-3127
09/01/2018
DOI: 10.1093/hmg/ddy237
PMCID: PMC6097157
PMID: 29931343
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.
Details
- Title: Subtitle
- Consortium-based genome-wide meta-analysis for childhood dental caries traits
- Creators
- Simon Haworth - Medical Research Council Integrative Epidemiology Unit at Bristol Medical School, University of Bristol, Bristol BS8 2BN, UKDmitry Shungin - Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USAJustin T van der Tas - Department of Oral and Maxillofacial Surgery, Special Dental Care and OrthodonticsStrahinja Vucic - Department of Oral and Maxillofacial Surgery, Special Dental Care and OrthodonticsCarolina Medina-Gomez - Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3015 CN, The NetherlandsVictor Yakimov - Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, DenmarkBjarke Feenstra - Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, DenmarkJohn R Shaffer - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USAMyoung Keun Lee - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USAMarie Standl - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg D-85764, GermanyElisabeth Thiering - Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich Medical Center, Munich 80337, GermanyCarol Wang - Division of Obstetrics and Gynaecology, The University of Western Australia, Perth WA 6009, AustraliaKlaus Bønnelykke - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, DenmarkJohannes Waage - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, DenmarkLeon Eyrich Jessen - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, DenmarkPia Elisabeth Nørrisgaard - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, DenmarkRaimo Joro - Institute of Biomedicine, School of Medicine, University of Eastern Finland Kuopio Campus, 70211 Kuopio, FinlandIlkka Seppälä - Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center Tampere - Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33520, FinlandOlli Raitakari - Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, FinlandTom Dudding - Medical Research Council Integrative Epidemiology Unit at Bristol Medical School, University of Bristol, Bristol BS8 2BN, UKOlja Grgic - The Generation R Study GroupEdwin Ongkosuwito - The Generation R Study GroupAnu Vierola - Institute of Biomedicine, School of Medicine, University of Eastern Finland Kuopio Campus, 70211 Kuopio, FinlandAino-Maija Eloranta - Institute of Biomedicine, School of Medicine, University of Eastern Finland Kuopio Campus, 70211 Kuopio, FinlandNicola X West - Bristol Dental School, University of Bristol, Bristol BS1 2LY, UKSteven J Thomas - Bristol Dental School, University of Bristol, Bristol BS1 2LY, UKDaniel W McNeil - Department of Psychology, Eberly College of Arts and Sciences, West Virginia University, Morgantown, WA 26506-6286, USASteven M Levy - Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Cedar Rapids, IA 52242-1010, USARebecca Slayton - Department of Pediatric Dentistry (Retired), School of Dentistry, University of Washington, Seattle, WA 98195, USAEllen A Nohr - Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkTerho Lehtimäki - Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center Tampere - Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33520, FinlandTimo Lakka - Kuopio Research Institute of Exercise Medicine, Kuopio 70100, FinlandHans Bisgaard - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofe Hospital, University of Copenhagen, Copenhagen 2730, DenmarkCraig Pennell - Division of Obstetrics and Gynaecology, The University of Western Australia, Perth WA 6009, AustraliaJan Kühnisch - Department of Conservative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians-Universität München, Munich 80336, GermanyMary L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USAMads Melbye - Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAFrank Geller - Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, DenmarkFernando Rivadeneira - Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3015 CN, The NetherlandsEppo B Wolvius - Department of Oral and Maxillofacial Surgery, Special Dental Care and OrthodonticsPaul W Franks - Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USAIngegerd Johansson - Department of Odontology, Umeå University, Umeå 901 87, SwedenNicholas J Timpson - Medical Research Council Integrative Epidemiology Unit at Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.27(17), pp.3113-3127
- DOI
- 10.1093/hmg/ddy237
- PMID
- 29931343
- PMCID
- PMC6097157
- NLM abbreviation
- Hum Mol Genet
- ISSN
- 1460-2083
- eISSN
- 1460-2083
- Publisher
- England
- Grant note
- R01 DE014899 / NIDCR NIH HHS U01 DE018903 / NIDCR NIH HHS Wellcome Trust R01 DE009551 / NIDCR NIH HHS 201237/Z/16/Z / Wellcome Trust R01 DE012101 / NIDCR NIH HHS P60 DE013076 / NIDCR NIH HHS HHSN268200782096C / NHGRI NIH HHS R03 DE024264 / NIDCR NIH HHS 076467/Z/05/Z / Wellcome Trust 202802/Z/16/Z / Wellcome Trust MOP-82893 / CIHR MC_UU_12013/3 / Medical Research Council
- Language
- English
- Date published
- 09/01/2018
- Academic Unit
- Preventive and Community Dentistry; Epidemiology; Pediatric Dentistry
- Record Identifier
- 9983917787402771
Metrics
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