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

Timpson, N. J., Tobias, J. H., Richards, J. B., Soranzo, N., Duncan, Emma L., Sims, A. M., Whittaker, P., Kumanduri, V., Zhai, G., Glaser, B., Eisman, J., Jones, G., Nicholson, G., Prince, R., Seeman, E., Spector, T. D., Brown, Matthew A., Peltonen, L., Smith, G. D., Deloukas, P., & Evans, D. M. (2009) 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.

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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.

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ID Code: 89404
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :61 Export Date: 21 September 2015 CODEN: HMGEE Correspondence Address: Evans, D.M.; MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Oakfield Grove, Bristol BS8 2BN, United Kingdom; email:
Keywords: DNA, transcription factor osterix, adult, article, body height, bone density, child, child growth, chromosome 12, controlled study, female, gene identification, gene locus, genetic association, genetic trait, genetic variability, genotype, hip, human, lumbar spine, male, priority journal, school child, single nucleotide polymorphism, Aged, Chromosomes, Human, Pair 12, Genome-Wide Association Study, Humans, Longitudinal Studies, Middle Aged, Polymorphism, Single Nucleotide, Transcription Factors
DOI: 10.1093/hmg/ddp052
ISSN: 0964-6906
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2009 The Author(s)
Deposited On: 22 Oct 2015 22:59
Last Modified: 22 Aug 2016 23:16

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