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

journal contribution
posted on 2023-05-17, 01:14 authored by Timpson, NJ, Tobias, JH, Richards, JB, Soranzo, N, Duncan, EL, Sims, AM, Whittaker, P, Kumanduri, V, Zhai, G, Glaser, B, Eisman, J, Graeme JonesGraeme Jones, Nicholson, G, Prince, R, Seeman, E, Spector, TD, Brown, MA, Peltonen, L, Davey Smith, G, Deloukas, P, Evans, DM
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).

History

Publication title

Human Molecular Genetics

Volume

18

Issue

8

Pagination

1510-1517

ISSN

0964-6906

Department/School

Menzies Institute for Medical Research

Publisher

Oxford Univ Press

Place of publication

Great Clarendon St, Oxford, England, Ox2 6Dp

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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