Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Fatemifar, Ghazaleh, Hoggart, Clive J., Paternoster, Lavinia, Kemp, John P., Prokopenko, Inga, Horikoshi, Momoko, Wright, Victoria J., Tobias, Jon H., Richmond, Stephen, Zhurov, Alexei I., Toma, Arshed M., Pouta, Anneli, Taanila, Anja, Sipila, Kirsi, Lahdesmaki, Raija, Pillas, Demetris, Geller, Frank, Feenstra, Bjarke, Melbye, Mads, Nohr, Ellen A., Ring, Susan M., St Pourcain, Beate, Timpson, Nicholas J., Smith, George D., Jarvelin, Marjo-Riitta and Evans, David M. (2013) Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances. Human Molecular Genetics, 22 18: 3807-3817. doi:10.1093/hmg/ddt231

Author Fatemifar, Ghazaleh
Hoggart, Clive J.
Paternoster, Lavinia
Kemp, John P.
Prokopenko, Inga
Horikoshi, Momoko
Wright, Victoria J.
Tobias, Jon H.
Richmond, Stephen
Zhurov, Alexei I.
Toma, Arshed M.
Pouta, Anneli
Taanila, Anja
Sipila, Kirsi
Lahdesmaki, Raija
Pillas, Demetris
Geller, Frank
Feenstra, Bjarke
Melbye, Mads
Nohr, Ellen A.
Ring, Susan M.
St Pourcain, Beate
Timpson, Nicholas J.
Smith, George D.
Jarvelin, Marjo-Riitta
Evans, David M.
Title Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1093/hmg/ddt231
Open Access Status DOI
Volume 22
Issue 18
Start page 3807
End page 3817
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
1312 Molecular Biology
Abstract Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studieswere combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 3 1028) for 'age at first tooth' and 11 loci for 'number of teeth'. Together, these associations explain 6.06% of the variation in 'age of first tooth' and 4.76% of the variation in 'number of teeth'. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P 5 9.080 3 10217). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Biochemistry & Molecular Biology
Genetics & Heredity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MRC G0800582
5R01MH63706: 02
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
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Created: Thu, 20 Mar 2014, 19:08:24 EST by Kylie Hengst on behalf of UQ Diamantina Institute