title: Common variants in the region around Osterix are associated with bone mineral density and growth in childhood.
abstract: 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.
authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Jon H
authors.initials: JH
authors.lastname: Tobias
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Emma L
authors.initials: EL
authors.lastname: Duncan
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Sims
authors.forename: Pamela
authors.initials: P
authors.lastname: Whittaker
authors.forename: Vasudev
authors.initials: V
authors.lastname: Kumanduri
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.forename: Beate
authors.initials: B
authors.lastname: Glaser
authors.forename: John
authors.initials: J
authors.lastname: Eisman
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.forename: Geoff
authors.initials: G
authors.lastname: Nicholson
authors.forename: Richard
authors.initials: R
authors.lastname: Prince
authors.forename: Ego
authors.initials: E
authors.lastname: Seeman
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
mesh_terms: 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*
chemical_list: D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors