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The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study
OBJECTIVE: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape. METHODS: Hip DXA scans, obtained in offspring from the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809624/ https://www.ncbi.nlm.nih.gov/pubmed/33285254 http://dx.doi.org/10.1016/j.bone.2020.115792 |
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author | Frysz, Monika Baird, Denis Gregory, Jenny S. Aspden, Richard M. Lane, Nancy E. Ohlsson, Claes Pettersson-Kymmer, Ulrika Karasik, David Tobias, Jonathan H. Paternoster, Lavinia |
author_facet | Frysz, Monika Baird, Denis Gregory, Jenny S. Aspden, Richard M. Lane, Nancy E. Ohlsson, Claes Pettersson-Kymmer, Ulrika Karasik, David Tobias, Jonathan H. Paternoster, Lavinia |
author_sort | Frysz, Monika |
collection | PubMed |
description | OBJECTIVE: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape. METHODS: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2. RESULTS: Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta −0.05, p = 9.9 × 10(−8); age 18: −0.05, p = 3.3 × 10(−6)) and HSM5 (age 14: beta −0.07, p = 1.6 × 10(−4); age 18: −0.1, p = 2.7 × 10(−6)). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 × 10(−5); age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: −0.06, p = 0.001; age 18: −0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture. CONCLUSION: In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life. |
format | Online Article Text |
id | pubmed-7809624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78096242021-02-01 The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study Frysz, Monika Baird, Denis Gregory, Jenny S. Aspden, Richard M. Lane, Nancy E. Ohlsson, Claes Pettersson-Kymmer, Ulrika Karasik, David Tobias, Jonathan H. Paternoster, Lavinia Bone Full Length Article OBJECTIVE: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape. METHODS: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2. RESULTS: Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta −0.05, p = 9.9 × 10(−8); age 18: −0.05, p = 3.3 × 10(−6)) and HSM5 (age 14: beta −0.07, p = 1.6 × 10(−4); age 18: −0.1, p = 2.7 × 10(−6)). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 × 10(−5); age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: −0.06, p = 0.001; age 18: −0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture. CONCLUSION: In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life. Elsevier Science 2021-02 /pmc/articles/PMC7809624/ /pubmed/33285254 http://dx.doi.org/10.1016/j.bone.2020.115792 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Full Length Article Frysz, Monika Baird, Denis Gregory, Jenny S. Aspden, Richard M. Lane, Nancy E. Ohlsson, Claes Pettersson-Kymmer, Ulrika Karasik, David Tobias, Jonathan H. Paternoster, Lavinia The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title | The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title_full | The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title_fullStr | The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title_full_unstemmed | The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title_short | The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study |
title_sort | influence of adult hip shape genetic variants on adolescent hip shape: findings from a population-based dxa study |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809624/ https://www.ncbi.nlm.nih.gov/pubmed/33285254 http://dx.doi.org/10.1016/j.bone.2020.115792 |
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