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

• Published in: Human molecular genetics Vol. 27; no. 17; pp. 3113 - 3127
• Main Authors: Haworth, Simon, Shungin, Dmitry, van der Tas, Justin T, Vucic, Strahinja, Medina-Gomez, Carolina, Yakimov, Victor, Feenstra, Bjarke, Shaffer, John R, Lee, Myoung Keun, Standl, Marie, Thiering, Elisabeth, Wang, Carol, Bønnelykke, Klaus, Waage, Johannes, Jessen, Leon Eyrich, Nørrisgaard, Pia Elisabeth, Joro, Raimo, Seppälä, Ilkka, Raitakari, Olli, Dudding, Tom, Grgic, Olja, Ongkosuwito, Edwin, Vierola, Anu, Eloranta, Aino-Maija, West, Nicola X, Thomas, Steven J, McNeil, Daniel W, Levy, Steven M, Slayton, Rebecca, Nohr, Ellen A, Lehtimäki, Terho, Lakka, Timo, Bisgaard, Hans, Pennell, Craig, Kühnisch, Jan, Marazita, Mary L, Melbye, Mads, Geller, Frank, Rivadeneira, Fernando, Wolvius, Eppo B, Franks, Paul W, Johansson, Ingegerd, Timpson, Nicholas J
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-09-2018
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adolescent; Arbetsmedicin och miljömedicin; Association Studies; Basic Medicine; Biomarkers - analysis; Case-Control Studies; Child; Child, Preschool; Dental Caries - genetics; Dentition, Permanent; Environmental Health and Occupational Health; Female; Genome-Wide Association Study - methods; Health Sciences; Humans; Hälsovetenskap; Male; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Phenotype; Phosphoproteins - genetics; Polymorphism, Single Nucleotide; Quantitative Trait Loci
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddy237

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.