Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.
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.
Pillas
Demetris
D
Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom.
Hoggart
Clive J
CJ
Evans
David M
DM
O'Reilly
Paul F
PF
Sipilä
Kirsi
K
Lähdesmäki
Raija
R
Millwood
Iona Y
IY
Kaakinen
Marika
M
Netuveli
Gopalakrishnan
G
Blane
David
D
Charoen
Pimphen
P
Sovio
Ulla
U
Pouta
Anneli
A
Freimer
Nelson
N
Hartikainen
Anna-Liisa
AL
Laitinen
Jaana
J
Vaara
Sarianna
S
Glaser
Beate
B
Crawford
Peter
P
Timpson
Nicholas J
NJ
Ring
Susan M
SM
Deng
Guohong
G
Zhang
Weihua
W
McCarthy
Mark I
MI
Deloukas
Panos
P
Peltonen
Leena
L
Elliott
Paul
P
Coin
Lachlan J M
LJ
Smith
George Davey
GD
Jarvelin
Marjo-Riitta
MR
D000483:Alleles; D004739:England; D005260:Female; D005387:Finland; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D015201:Meta-Analysis as Topic; D036801:Parturition; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014078:Tooth Eruption / Q000235:genetics; D014094:Tooth, Deciduous / Q000254:growth & development*