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Common variants in the region around Osterix are associated with bone mineral density and growth in childhood


Timpson, NJ and Tobias, JH and Richards, JB and Soranzo, N and Duncan, EL and Sims, AM and Whittaker, P and Kumanduri, V and Zhai, G and Glaser, B and Eisman, J and Jones, G and Nicholson, G and Prince, R and Seeman, E and Spector, TD and Brown, MA and Peltonen, L and Davey Smith, G and Deloukas, P and Evans, DM, Common variants in the region around Osterix are associated with bone mineral density and growth in childhood, Human Molecular Genetics, 18, (8) pp. 1510-1517. ISSN 0964-6906 (2009) [Refereed Article]

DOI: doi:10.1093/hmg/ddp052


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 × 10-4; Australia: P = 3.7 × 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 × 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 × 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. © 2009 The Author(s).

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Jones, G (Professor Graeme Jones)
ID Code:60406
Year Published:2009
Web of Science® Times Cited:104
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-02-03
Last Modified:2010-04-16

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