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Genetic and environmental determinants of primary tooth eruption

Background: Primary tooth eruption is a complex and highly regulated process through which primary teeth enter the mouth and become visible. Along with many other aspects of development, genes are thought to explain a large proportion of the variation in primary tooth eruption, although environmental factors are also thought to contribute. The aim of this thesis was to investigate the genetic and environmental determinants of primary tooth eruption. Methods: The majority of analyses carried out in this thesis were based on data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC). Initially a series of observational analyses were conducted to examine the relationship between several early life exposures and primary tooth eruption (assessed at 15 months) in 7,445 individuals from ALSPAC. I then examined whether primary tooth eruption was related to future anthropometric measures in a longitudinal sample of 2,977 individuals at 17 years. In order to identify genetic variants involved in primary tooth eruption I performed a population based genome-wide association (GWA) meta-analysis of 'age at first tooth' and 'number of teeth' using 5,998 and 6,609 individuals respectively from ALSPAC and 5, 120 and 4,904 individuals respectively from the 1966 Northern Finland Birth Cohort (NFBC 1966). Finally, I examined whether the relationships previously established between primary tooth eruption and anthropometric measures at adolescence were a consequence of genetic and/or environmental factors, by carrying out a series of analyses using allelic scores and Genetic Complex Trait Analysis (GCTA). Results: Several early life factors were associated with primary tooth eruption including birth weight, breastfeeding and maternal smoking, which failed to attenuate after adjustment for confounding (including patiner smoking). 'Number of teeth' was positively associated with height (males only), weight and fat mass at 17 years in fully adjusted models. In genetic analyses, 15 independent loci (including 8 novel variants) were associated with primary tooth eruption (p<5xlO-8 ) . These loci overlapped genes previously implicated in tooth development, generalised growth and/or cancer. Together these variants explained approximately 6.1 % of the variation in 'age of first tooth' and 4.8% of the variation in 'number of teeth'. There was little evidence to suggest that variants associated with tooth eruption at genome-wide significant levels had pleiotropic effects on height, weight, fat mass or lean mass. However, several previously robustly associated height SNPs were also associated with primary tooth eruption. Bivariate GCT A analyses provided fm1her evidence for this relationship through the estimation of a negative genetic correlation between 'age at first tooth' and height. Conclusions: Several early life factors were related to primary tooth eruption. The association between maternal smoking during pregnancy and primary tooth eruption was consistent with an intrauterine effect. Primary tooth eruption was also associated with future anthropometric measures of growth and development, with early eruption related to the development of adiposity in later life. GCTA and genetic association analyses identified several novel genetic variants associated with primary tooth eruption and suggest that at least pa11 of the relationship between eruption and anthropometric measures at later ages is a result of genetic factors.
Date January 2013
CreatorsFatemifar, Ghazaleh
PublisherUniversity of Bristol
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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