Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

Demetris Pillas(Economic and Social Research Council), Clive Hoggart(Imperial College London), David M. Evans(University of Bristol), Paul F. O’Reilly(Imperial College London), Kirsi Sipilä(Oulu University Hospital), Raija Lähdesmäki(Oulu University Hospital), Iona Y. Millwood(University of Oxford), Marika Kaakinen(University of Oulu), Gopalakrishnan Netuveli(Economic and Social Research Council), David Blane(Economic and Social Research Council), Pimphen Charoen(Mahidol University), Ulla Sovio(Imperial College London), Anneli Pouta(Finnish Institute for Health and Welfare), Nelson Freimer(University of California, Los Angeles), Anna‐Liisa Hartikainen(University of Oulu), Jaana Laitinen(Finnish Institute of Occupational Health), Sarianna Vaara(Finnish Institute for Health and Welfare), Beate Glaser(University of Bristol), P J Crawford(University Of Bristol Dental Hospital), Nicholas J. Timpson(University of Bristol), Susan M. Ring(University of Bristol), Guohong Deng(Imperial College London), Weihua Zhang(Imperial College London), Mark I. McCarthy(Centre for Human Genetics), Panos Deloukas(Wellcome Sanger Institute), Leena Peltonen(University of Helsinki), Paul Elliott(Imperial College London), Lachlan Coin(Imperial College London), George Davey Smith(University of Bristol), Marjo‐Riitta Järvelin(Finnish Institute for Health and Welfare)
PLoS Genetics
February 26, 2010
10.1371/journal.pgen.1000856
Cited by 92Open Access
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Abstract

Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5x10(-8), and 5 with suggestive association (P<5x10(-6)). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.

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