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

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; Paul W. Franks; Ingegerd Johansson; Nicholas J. Timpson

doi:10.1093/hmg/ddy237

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

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 DuddingOlja 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, Paul W. Franks, Ingegerd Johansson, Nicholas J. Timpson

^*Corresponding author for this work

Department of Clinical Medicine

10 Citations (Scopus)

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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.

Original language	English
Journal	Human Molecular Genetics
Volume	27
Issue number	17
Pages (from-to)	3113-3127
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddy237
Publication status	Published - 1 Sept 2018

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Haworth, S., Shungin, D., Van Der Tas, J. T., Vucic, S., Medina-Gomez, C., Yakimov, V., Feenstra, B., Shaffer, J. R., Lee, M. K., Standl, M., Thiering, E., Wang, C., Bønnelykke, K., Waage, J., Jessen, L. E., Nørrisgaard, P. E., Joro, R., Seppälä, I., Raitakari, O., ... Timpson, N. J. (2018). Consortium-based genome-wide meta-analysis for childhood dental caries traits. Human Molecular Genetics, 27(17), 3113-3127. https://doi.org/10.1093/hmg/ddy237

Haworth, S, Shungin, D, Van Der Tas, JT, Vucic, S, Medina-Gomez, C, Yakimov, V, Feenstra, B, Shaffer, JR, Lee, MK, Standl, M, Thiering, E, Wang, C, Bønnelykke, K, Waage, J, Jessen, LE, Nørrisgaard, PE, Joro, R, Seppälä, I, Raitakari, O, Dudding, T, Grgic, O, Ongkosuwito, E, Vierola, A, Eloranta, AM, West, NX, Thomas, SJ, McNeil, DW, Levy, SM, Slayton, R, Nohr, EA, Lehtimäki, T, Lakka, T, Bisgaard, H, Pennell, C, Kühnisch, J, Marazita, ML, Melbye, M, Geller, F, Rivadeneira, F, Wolvius, EB, Franks, PW, Johansson, I & Timpson, NJ 2018, 'Consortium-based genome-wide meta-analysis for childhood dental caries traits', Human Molecular Genetics, vol. 27, no. 17, pp. 3113-3127. https://doi.org/10.1093/hmg/ddy237

@article{c3da1f3553ee4ba1872fa603cdc1dde3,

title = "Consortium-based genome-wide meta-analysis for childhood dental caries traits",

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.",

author = "Simon Haworth and Dmitry Shungin and {Van Der Tas}, {Justin T.} and Strahinja Vucic and Carolina Medina-Gomez and Victor Yakimov and Bjarke Feenstra and Shaffer, {John R.} and Lee, {Myoung Keun} and Marie Standl and Elisabeth Thiering and Carol Wang and Klaus B{\o}nnelykke and Johannes Waage and Jessen, {Leon Eyrich} and N{\o}rrisgaard, {Pia Elisabeth} and Raimo Joro and Ilkka Sepp{\"a}l{\"a} and Olli Raitakari and Tom Dudding and Olja Grgic and Edwin Ongkosuwito and Anu Vierola and Eloranta, {Aino Maija} and West, {Nicola X.} and Thomas, {Steven J.} and McNeil, {Daniel W.} and Levy, {Steven M.} and Rebecca Slayton and Nohr, {Ellen A.} and Terho Lehtim{\"a}ki and Timo Lakka and Hans Bisgaard and Craig Pennell and Jan K{\"u}hnisch and Marazita, {Mary L.} and Mads Melbye and Frank Geller and Fernando Rivadeneira and Wolvius, {Eppo B.} and Franks, {Paul W.} and Ingegerd Johansson and Timpson, {Nicholas J.}",

year = "2018",

month = sep,

day = "1",

doi = "10.1093/hmg/ddy237",

language = "English",

volume = "27",

pages = "3113--3127",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "17",

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TY - JOUR

T1 - Consortium-based genome-wide meta-analysis for childhood dental caries traits

AU - Haworth, Simon

AU - Shungin, Dmitry

AU - Van Der Tas, Justin T.

AU - Vucic, Strahinja

AU - Medina-Gomez, Carolina

AU - Yakimov, Victor

AU - Feenstra, Bjarke

AU - Shaffer, John R.

AU - Lee, Myoung Keun

AU - Standl, Marie

AU - Thiering, Elisabeth

AU - Wang, Carol

AU - Bønnelykke, Klaus

AU - Waage, Johannes

AU - Jessen, Leon Eyrich

AU - Nørrisgaard, Pia Elisabeth

AU - Joro, Raimo

AU - Seppälä, Ilkka

AU - Raitakari, Olli

AU - Dudding, Tom

AU - Grgic, Olja

AU - Ongkosuwito, Edwin

AU - Vierola, Anu

AU - Eloranta, Aino Maija

AU - West, Nicola X.

AU - Thomas, Steven J.

AU - McNeil, Daniel W.

AU - Levy, Steven M.

AU - Slayton, Rebecca

AU - Nohr, Ellen A.

AU - Lehtimäki, Terho

AU - Lakka, Timo

AU - Bisgaard, Hans

AU - Pennell, Craig

AU - Kühnisch, Jan

AU - Marazita, Mary L.

AU - Melbye, Mads

AU - Geller, Frank

AU - Rivadeneira, Fernando

AU - Wolvius, Eppo B.

AU - Franks, Paul W.

AU - Johansson, Ingegerd

AU - Timpson, Nicholas J.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddy237

DO - 10.1093/hmg/ddy237

M3 - Journal article

C2 - 29931343

AN - SCOPUS:85055418212

SN - 0964-6906

VL - 27

SP - 3113

EP - 3127

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 17

ER -

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

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