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

Pillas, D; Hoggart, CJ; Evans, DM; O'Reilly, PF; Sipila, K; Lahdesmaki, R; Millwood, IY; ... Jarvelin, MR; + view all (2010) Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy. PLOS GENET , 6 (2) , Article e1000856. 10.1371/journal.pgen.1000856. Green open 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.

Type: Article
Title: Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1000856
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1000856
Language: English
Additional information: © 2010 Pillas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The NFBC1966 received financial support from the Academy of Finland (project grants 104781, 120315, 132797, and Center of Excellence in Complex Disease Genetics); University Hospital Oulu, Biocenter, University of Oulu, Finland; the European Community's Fifth/Seventh Framework Programme (EURO-BLCS, QLG1-CT-2000-01643, FP7/2007-2013); NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01); ENGAGE project (HEALTH-F4-2007-201413); the Medical Research Council (studentship grant G0500539, centre grant G0600705); the Wellcome Trust (project grant GR069224), UK; the Research Council UK fellowship; the National Institute of Health Research (NIHR) Biomedical Research Centre Programme at Imperial College; and the Division of Epidemiology, Public Health and Primary Care (studentship grant DFHM G24038). The DNA extractions, sample quality controls, biobank up-keeping, and aliquotting were performed in the National Public Health Institute, Biomedicum Helsinki, Finland, and supported financially by the Academy of Finland and Biocentrum Helsinki. The UK Medical Research Council, the Wellcome Trust, and the University of Bristol provide core support for ALSPAC. CJH is funded by a European Union grant HEALTH-2007-201550 HyperGenes. DME is supported by a Medical Research Council New Investigator Award (MRC G0800582). The ICLS (International Centre for Life Course Studies in Society and Health) is funded by an ESRC award: RES-596-28-0001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: COMMON VARIANTS, BREAST-CANCER, MESSENGER-RNA, POPULATION, COHORT, GENES, TEETH, IDENTIFICATION, MICROARRAY, EXPRESSION
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
URI: https://discovery.ucl.ac.uk/id/eprint/1389824
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