Genome-wide association study reveals multiple loci associated with primary tooth development during infancy

PLoS Genet. 2010 Feb 26;6(2):e1000856. doi: 10.1371/journal.pgen.1000856.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • England
  • Female
  • Finland
  • Genetic Loci / genetics*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Infant
  • Linkage Disequilibrium / genetics
  • Longitudinal Studies
  • Male
  • Meta-Analysis as Topic
  • Parturition
  • Polymorphism, Single Nucleotide / genetics
  • Tooth Eruption / genetics
  • Tooth, Deciduous / growth & development*