Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.
Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 x 10(-4); Australia: P = 3.7 x 10(-4)). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 x 10(-11)). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 x 10(-5)). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.
Timpson
Nicholas J
NJ
MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK.
Tobias
Jon H
JH
Richards
J Brent
JB
Soranzo
Nicole
N
Duncan
Emma L
EL
Sims
Anne-Marie
AM
Whittaker
Pamela
P
Kumanduri
Vasudev
V
Zhai
Guangju
G
Glaser
Beate
B
Eisman
John
J
Jones
Graeme
G
Nicholson
Geoff
G
Prince
Richard
R
Seeman
Ego
E
Spector
Tim D
TD
Brown
Matthew A
MA
Peltonen
Leena
L
Smith
George Davey
GD
Deloukas
Panos
P
Evans
David M
DM
D000368:Aged; D001827:Body Height / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D002648:Child; D002881:Chromosomes, Human, Pair 12; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*
D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors