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

Fatemifar, Ghazelah, Hoggart, Clive J., Paternoster, Lavinia, Kemp, John P., Prokopenko, Inga, Horikoshi, Momoko, Wright, Victoria J., Tobias, Jon H., Richmond, Stephen, Zhurov, Alexei, 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., Davey Smith, George, 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) , pp. 3807-3817. 10.1093/hmg/ddt231

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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 studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven 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 a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RK Dentistry
Publisher: Oxford University Press
ISSN: 0964-6906
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 05:01
URI: http://orca.cf.ac.uk/id/eprint/47535

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