Genetic variants in adult bone mineral density and fracture risk genes are associated with the rate of bone mineral density acquisition in adolescence

Warrington, Nicole M., Kemp, John P., Tilling, Kate, Tobias, Jonathan H. and Evans, David M. (2015) Genetic variants in adult bone mineral density and fracture risk genes are associated with the rate of bone mineral density acquisition in adolescence. Human Molecular Genetics, 24 14: 4158-4166. doi:10.1093/hmg/ddv143


Author Warrington, Nicole M.
Kemp, John P.
Tilling, Kate
Tobias, Jonathan H.
Evans, David M.
Title Genetic variants in adult bone mineral density and fracture risk genes are associated with the rate of bone mineral density acquisition in adolescence
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2015-05-04
Year available 2015
Sub-type Article (original research)
DOI 10.1093/hmg/ddv143
Open Access Status Not yet assessed
Volume 24
Issue 14
Start page 4158
End page 4166
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
Abstract Previous studies have identified 63 single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) in adults. These SNPs are thought to reflect variants that influence bone maintenance and/or loss in adults. It is unclear whether they affect the rate of bone acquisition during adolescence. Bone measurements and genetic data were available on 6397 individuals from the Avon Longitudinal Study of Parents and Children at up to five follow-up clinics. Linear mixed effects models with smoothing splines were used for longitudinal modelling of BMD and its components bone mineral content (BMC) and bone area (BA), from 9 to 17 years. Genotype data from the 63 adult BMD associated SNPs were investigated individually and as a genetic risk score in the longitudinal model. Each additional BMD lowering allele of the genetic risk score was associated with lower BMD at age 13 [per allele effect size, 0.002 g/cm(2) (SE = 0.0001, P = 1.24 × 10(-38))] and decreased BMD acquisition from 9 to 17 years (P = 9.17 × 10(-7)). This association was driven by changes in BMC rather than BA. The genetic risk score explained ∼2% of the variation in BMD at 9 and 17 years, a third of that explained in adults (6%). Genetic variants that putatively affect bone maintenance and/or loss in adults appear to have a small influence on the rate of bone acquisition through adolescence.
Formatted abstract
Previous studies have identified 63 single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) in adults. These SNPs are thought to reflect variants that influence bone maintenance and/or loss in adults. It is unclear whether they affect the rate of bone acquisition during adolescence. Bone measurements and genetic data were available on 6397 individuals from the Avon Longitudinal Study of Parents and Children at up to five follow-up clinics. Linear mixed effects models with smoothing splines were used for longitudinal modelling of BMD and its components bone mineral content (BMC) and bone area (BA), from 9 to 17 years. Genotype data from the 63 adult BMD associated SNPs were investigated individually and as a genetic risk score in the longitudinal model. Each additional BMD lowering allele of the genetic risk score was associated with lower BMD at age 13 [per allele effect size, 0.002 g/cm2 (SE = 0.0001, P = 1.24 × 10-38)] and decreased BMD acquisition from 9 to 17 years (P = 9.17 × 10-7). This association was driven by changes in BMC rather than BA. The genetic risk score explained ~2% of the variation in BMD at 9 and 17 years, a third of that explained in adults (6%). Genetic variants that putatively affect bone maintenance and/or loss in adults appear to have a small influence on the rate of bone acquisition through adolescence
Keyword Genome wide association
Longitudinal data
Femoral neck
Mixed model
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 102215
MC_PC_15018
102215/2/13/2
MC_UU_12013/4
MC_UU_12013/9
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
 
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Created: Thu, 16 Jul 2015, 23:00:52 EST by Nicole Warrington on behalf of UQ Diamantina Institute