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 Chil...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Oxford University Press (OUP)
2012
|
| Online Access: | http://hdl.handle.net/1721.1/73094 |
| _version_ | 1826217173151907840 |
|---|---|
| author | Peltonen, Leena Timpson, Nicholas J. Tobias, Jon H. Richards, J. Brent Soranzo, Nicole Duncan, Emma L. Sims, Anne-Marie Whittaker, Pamela Kumanduri, Vasudev Zhai, Guangju Glaser, Beate Eisman, John Jones, Graeme Nicholson, Geoff Prince, Richard Seeman, Ego Spector, Tim D. Brown, Matthew A. Davey-Smith, George Deloukas, Panos Evans, David M. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Peltonen, Leena Timpson, Nicholas J. Tobias, Jon H. Richards, J. Brent Soranzo, Nicole Duncan, Emma L. Sims, Anne-Marie Whittaker, Pamela Kumanduri, Vasudev Zhai, Guangju Glaser, Beate Eisman, John Jones, Graeme Nicholson, Geoff Prince, Richard Seeman, Ego Spector, Tim D. Brown, Matthew A. Davey-Smith, George Deloukas, Panos Evans, David M. |
| author_sort | Peltonen, Leena |
| collection | MIT |
| description | 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[superscript −4]; Australia: P = 3.7 × 10[superscript −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[superscript −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[superscript −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. |
| first_indexed | 2024-09-23T16:59:12Z |
| format | Article |
| id | mit-1721.1/73094 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:59:12Z |
| publishDate | 2012 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/730942022-10-03T09:36:04Z Common variants in the region around Osterix are associated with bone mineral density and growth in childhood Peltonen, Leena Timpson, Nicholas J. Tobias, Jon H. Richards, J. Brent Soranzo, Nicole Duncan, Emma L. Sims, Anne-Marie Whittaker, Pamela Kumanduri, Vasudev Zhai, Guangju Glaser, Beate Eisman, John Jones, Graeme Nicholson, Geoff Prince, Richard Seeman, Ego Spector, Tim D. Brown, Matthew A. Davey-Smith, George Deloukas, Panos Evans, David M. Broad Institute of MIT and Harvard Peltonen, Leena 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[superscript −4]; Australia: P = 3.7 × 10[superscript −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[superscript −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[superscript −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. 2012-09-21T12:56:22Z 2012-09-21T12:56:22Z 2009-01 2009-01 Article http://purl.org/eprint/type/JournalArticle 0964-6906 1460-2083 http://hdl.handle.net/1721.1/73094 Timpson, N. J. et al. “Common Variants in the Region Around Osterix Are Associated with Bone Mineral Density and Growth in Childhood.” Human Molecular Genetics 18.8 (2009): 1510–1517. en_US http://dx.doi.org/10.1093/hmg/ddp052 Human Molecular Genetics Creative Commons Attribution Non-Commercial http://creativecommons.org/licenses/by-nc/2.5 application/pdf Oxford University Press (OUP) Oxford |
| spellingShingle | Peltonen, Leena Timpson, Nicholas J. Tobias, Jon H. Richards, J. Brent Soranzo, Nicole Duncan, Emma L. Sims, Anne-Marie Whittaker, Pamela Kumanduri, Vasudev Zhai, Guangju Glaser, Beate Eisman, John Jones, Graeme Nicholson, Geoff Prince, Richard Seeman, Ego Spector, Tim D. Brown, Matthew A. Davey-Smith, George Deloukas, Panos Evans, David M. Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title | Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title_full | Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title_fullStr | Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title_full_unstemmed | Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title_short | Common variants in the region around Osterix are associated with bone mineral density and growth in childhood |
| title_sort | common variants in the region around osterix are associated with bone mineral density and growth in childhood |
| url | http://hdl.handle.net/1721.1/73094 |
| work_keys_str_mv | AT peltonenleena commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT timpsonnicholasj commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT tobiasjonh commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT richardsjbrent commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT soranzonicole commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT duncanemmal commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT simsannemarie commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT whittakerpamela commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT kumandurivasudev commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT zhaiguangju commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT glaserbeate commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT eismanjohn commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT jonesgraeme commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT nicholsongeoff commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT princerichard commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT seemanego commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT spectortimd commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT brownmatthewa commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT daveysmithgeorge commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT deloukaspanos commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood AT evansdavidm commonvariantsintheregionaroundosterixareassociatedwithbonemineraldensityandgrowthinchildhood |