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Oxford University Press, Human Molecular Genetics, 18(22), p. 3807-3817, 2013

DOI: 10.1093/hmg/ddt231

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

Journal article published in 2013 by Ghazaleh Fatemifar, Clive J. Hoggart, Lavinia Paternoster ORCID, John P. Kemp, Inga Prokopenko ORCID, Momoko Horikoshi, Victoria J. Wright, Jon H. Tobias ORCID, Stephen Richmond, Alexei I. Zhurov, Arshed M. Toma, Anneli Pouta, Anja Taanila, Kirsi Sipila, Raija Lähdesmäki and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.